UTI Slides 2024.pdf

Urinary Tract Infections CAS 805: Pharmacotherapy III Justin R. Lenhard  Outline Pathogenesis Microbiology Presentation: Complicated versus Uncomplicated, Cystitis versus Pyelonephritis Treatment: Uncomplicated UTIs Treatment: Complicated UTIs Pathophysiology Pye...

Urinary Tract Infections CAS 805: Pharmacotherapy III Justin R. Lenhard  Outline Pathogenesis Microbiology Presentation: Complicated versus Uncomplicated, Cystitis versus Pyelonephritis Treatment: Uncomplicated UTIs Treatment: Complicated UTIs Pathophysiology Pyelonephritis Cystitis http://www.liftlaughkegel.com/blog/2015/8/21/7-things-you-need-to-know-about-utis  UTI Risk Factors (many) Image result for kidney stone Structural abnormalities Obstructions Anatomical dysfunction Catheterization Transplantation Pregnancy T2DM Hx of recurrent UTIs Use of spermicides and diaphragms Frequent/recent sexual intercourse  Outline Pathogenesis Microbiology Presentation: Complicated versus Uncomplicated, Cystitis versus Pyelonephritis Treatment: Uncomplicated UTIs Treatment: Complicated UTIs  Microbiology Uncomplicated UTIs: Escherichia coli >> Proteus, Klebsiella (PEK), Staph. saprophyticus Complicated UTIs: PEK, Candida species, Pseudomonas aeruginosa, Enterococcus Contaminants during urine collection: Lactobacillus, Propionibacterium Microbiology  Outline Pathogenesis Microbiology Presentation: Complicated versus Uncomplicated, Cystitis versus Pyelonephritis Treatment: Uncomplicated UTIs Treatment: Complicated UTIs  Cystitis versus Pyelonephritis Cystitis Urinary frequency, urgency, dysuria ± pyuria or hematuria Pyelonephritis Cystitis symptoms + flank pain, fever, chills, leukocytosis Elderly/catheterized patients may have other symptoms like altered mental status Complicated UTIs Increased risk of failing therapy. Possible examples include: Diabetes Pregnancy Symptoms >7 days before getting care Hospital acquired UTI Renal failure or renal transplantation/immunocompromised Urinary tract obstruction Urinary catheterization/stent Functional/anatomical abnormalities Male gender usually considered criteria for complicated UTI Diagnosis UTIs Pyuria (WBCs in urine) does not mean someone has a UTI, but the absence of pyuria may help to rule out a UTI Uncomplicated cystitis often diagnosed based on symptoms/history of prior UTIs Pyelonephritis/complicated UTIs should always have a urinalysis/urinary culture. ≥105 CFU/mL = bacteriuria. ≥102 CFU/mL + symptoms = UTI UTIs Urinalysis Nitrites from enteric bacteria metabolism Leukocyte esterase from activated WBCs Pyuria > 10 WBCs per mm3 Bacteria in urine (not quantified)  Outline Pathogenesis Microbiology Presentation: Complicated versus Uncomplicated, Cystitis versus Pyelonephritis Treatment: Uncomplicated UTIs Treatment: Complicated UTIs  Uncomplicated Cystitis: 1st Line Nitrofurantoin 100 mg PO bid x 5 days CI CrCl < 30 ml/min Narrow spectrum, great for stewardship Don’t use if pyelonephritis suspected SE: peripheral neuropathy, GI, brown urine, well tolerated generally Trim/sulfa 160/800 mg (DS) PO bid x 3 days Do not use if local susceptibility is less than 80% Do not use if Bactrim used in last 3 months and susceptibility unknown Sulfa allergy, hematologic, increased K+ (trimethoprim), GI Antibiogram provided by Nicola Clayton, PharmD  Uncomplicated Cystitis: 2nd Line Fosfomycin 3 g PO x 1 dose Do not use if pyelonephritis suspected Bacterial efficacy inferior to 1st line agents Great for stewardship  Uncomplicated Cystitis: 3rd Line Ciprofloxacin PO, Levofloxacin PO x 3 days Anti-pseudomonal agents for uncomplicated cystitis? Come on people! Overuse is decreasing their efficacy. Don’t use if >10% of common uropathogens are resistant Reserved if 1st and 2nd line therapies are not viable PO β-Lactams (Augmentin, PO cephalosporins) x 3 - 7d Don’t use amoxicillin/ampicillin due to resistance Often inferior to 1st line agents Confirming susceptibilities is useful for these agents Antibiogram provided by Nicola Clayton, PharmD  Ambiguous Terminology in Practice In clinical practice, some prescribers treat every pyelonephritis infection as if it is a complicated UTI, and patients without systemic signs of infection that are traditionally considered complicated (men, poorly controlled T2DM, urologic abnormalities) may be treated as if they have uncomplicated UTIs. This is just a clinical aside, for exams/applications assume men = complicated UTIs for consistency  Uncomplicated Pyelonephritis Pyelonephritis is a more serious infection than cystitis Even in outpatient setting, urine cultures are recommended Outpatient treatment is usually acceptable for patients tolerating PO fluids and antibiotics if they are stable. If patient presents at ED may get IV dose x 1 and 12h monitoring 1st. Hospitalize if severely ill with marked fever, pain, debility, inability to take PO medications/fluids, or compliance issues  Uncomplicated Pyelonephritis: 1st Line Ciprofloxacin 500 mg PO bid or Cipro ER 1 g daily x 7d Levofloxacin 750 mg PO daily x 7 days Caution if >10% local resistance or recent quinolone use IV dose of ceftriaxone or an aminoglycoside before discharging as outpatient if susceptibility unknown Uncomplicated Pyelonephritis: 2nd Line Trim/Sulfa 160/800 mg PO bid x 14 days IV dose of ceftriaxone of an aminoglycoside before discharging as outpatient if susceptibility unknown Used if quinolone intolerance or quinolone resistance Uncomplicated Pyelonephritis: 3rd Line IV β-Lactams Intolerance/resistance to quinolones and Bactrim PO β-Lactams Use generally discouraged If confirmed susceptibility may consider 14 day treatment Do not use: nitrofurantoin or fosfomycin due to poor concentrations in renal tissue Uncomp. Pyelonephritis: Hospitalization Initial therapy for an acutely sick patient with pyelonephritis requiring hospitalization may vary between empiric IV broad spectrum β-lactams, fluoroquinolones, and aminoglycosides based on local susceptibilities, followed by antimicrobial de- escalation based on cultures and eventual PO conversion when the patient is stable and tolerates PO fluids/medication Painful Urination - Analgesia Phenazopyridine (Pyridium, Azo Urinary Pain Relief) – OTC 200 mg PO TID x 2 days Take with food and full glass of water CI in renal or liver impairment May cause red-orange coloring of the urine and other bodily fluids  Outline Pathogenesis Microbiology Presentation: Complicated versus Uncomplicated, Cystitis versus Pyelonephritis Treatment: Uncomplicated UTIs Treatment: Complicated UTIs Complicated UTIs Increased risk of failing therapy. Possible examples include: Diabetes Pregnancy Symptoms >7 days before getting care Hospital acquired UTI Renal failure or renal transplantation Urinary tract obstruction Urinary catheterization/stent Functional/anatomical abnormalities Male gender usually considered criteria for complicated UTI Complicated UTIs Always get urine cultures for complicated UTIs prior to starting antibiotics Gram-stain can rule out S. aureus and Enterococci CT scans or renal ultrasounds may be used to detect urinary obstructions for severely ill patients or patients that are not responding to therapy. Urologic consults necessary if obstruction detected. Complicated Cystitis (outpatient) Often receive 1 dose of IV ceftriaxone, ertapenem, or an aminoglycoside and then: PO Ciprofloxacin or Levofloxacin Trimethoprim-Sulfamethoxazole Possibly Amoxicillin-Clavulanic Acid or Cefpodoxime if high rates of resistance to above agents Complicated UTIs (inpatient) Complicated pyelonephritis should always start as inpatient therapy. Empiric therapy based on patient risk factors: Commonly Used Agents Patient Population Ceftriaxone 1 gram IV q24h Low risk MDR and not critically ill Ciprofloxacin or Levofloxacin Piperacillin-Tazobactam Need Pseudomonal coverage Cefepime Critically ill or high risk of ESBL- Carbapenem producers Risk of Enterococcus sp. based on Possibly add Vancomycin (or Ampicillin) prior cultures Complicated UTIs (inpatient) Refine initial therapy based on urine culture results May switch to an appropriate PO option based on patient response and susceptibility report (remember that nitrofurantoin can only be used for cystitis) Duration of therapy is based on patient response and agent selected: Quinolones + quick response = 5 – 7 days Other agents = 7 – 10 days  ESBL-Producing Enterobacterales Enterobacterales vary in the types of β-lactamase enzymes they produce. Some isolates may not produce any enzymes, some may produce narrow-spectrum enzymes that hydrolyze aminopenicillins, and some pay produce extended-spectrum β-lactamase (ESBL) enzymes that hydrolyze third generation cephalosporins Common ESBL-producers are: E. coli, K. pneumoniae, and other Enterobacterales Per the IDSA, the drugs of choice for Enterobacterale that produce an ESBL enzyme depend on whether the organisms are exclusively in the urinary tract: Uncomplicated Pyelonephritis and Bacteria are Outside of the Cystitis Complicated UTIs Urinary Tract Nitrofurantoin and Trim-Sulfa, Carbapenems (mero/imi Drugs of Choice Trim-Sulfa Cipro/Levofloxacin preferred if critically ill) Carbapenems, PO step down to Trim-Sulfa, Cipro/Levofloxacin, Carbapenems, Alternatives Cipro/ Levofloxacin if Aminoglycosides, Aminoglycosides appropriate Fosfomycin Antibiogram provided by Nicola Clayton, PharmD Asymptomatic Bacteriuria (ASB) IDSA Updated their Guidelines in 2019 Do Screen for ASB No Recommendation Do NOT Screen for ASB Pregnant Women High Risk Neutropenia* Delirium/falls** Urologic Procedures (1 – Indwelling Catheter Everyone else not in the 2 doses prior) Removal chart! * High risk = ANC < 100 for ≥ 7 days following chemotherapy ** For elderly patients with cognitive impairment/delirium or who experience a ground level fall without UTI symptoms, the IDSA recommends assessment for other causes and careful observation instead of treatment for ASB. Pregnancy All pregnant women should receive a urinalysis early in pregnancy to screen for bacteriuria ~12 – 16 weeks gestation ≥105 CFU/mL with no symptoms = asymptomatic bacteriuria. Must treat in pregnant women! Pregnancy Antibiotics to avoid in pregnancy: Quinolones and tetracyclines (always avoid) Ceftriaxone causes biliary displacement in neonates, avoid near term Hypothetical fetal risk with imipenem-cilastatin? Nitrofurantoin appears to be safe, but one study found an association with birth defects. Standard of care is to not use nitrofurantoin in the 1st trimester or at term (due to hemolytic anemia risk) if it can be avoided Trimethoprim is a folic acid antagonist avoided in the 1st trimester, and sulfonamides have a hypothetical bilirubin displacement risk in neonates, thus Bactrim is only used in mid-pregnancy Aminoglycosides may be associated with fetal ototoxicity Pregnancy: Bacteriuria or Cystitis Options include: PO cefpodoxime PO Augmentin PO fosfomycin (1 dose, IDSA says there is limited evidence) Nitrofurantoin (hypothetical risk in 1st trimester?, OK if 2nd or 3rd trimester) Treat 4 – 7 days (fosfomycin is a single dose). Repeat culture for test of cure, then monthly urine cultures until delivery to rule out recurrence Pregnancy: Pyelonephritis Treated with intravenous antibiotics until mother is afebrile for 24 – 48h, then PO conversion and discharge likely Treatment with 3rd generation cephalosporin if mild – moderate severity, or Zosyn/Carbapenems (not imipenem) if severe. Aztreonam if penicillin allergy. PO options are mostly β-lactams, but Bactrim is an option in the second trimester (nitrofurantoin and fosfomycin are not used in pyelonephritis). Total treatment duration is 7 – 10 days. UTIs: What should I know? Know the difference between uncomplicated versus complicated UTIs, and cystitis versus pyelonephritis Know the criteria to distinguish uncomplicated vs. complicated Know the PO options and dosing for uncomplicated cystitis Know the PO options and dosing for uncomplicated pyelonephritis Have a general idea of the IV options for complicated UTIs Know which antibiotics are safe to use in pregnancy Know that bacteriuria is treated in pregnancy Know the durations of treatment for uncomplicated UTIs, general idea for complicated UTIs Know the microbiology of UTIs  IDSA Guidelines IDSA has three sets of guidelines related to UTIs and bacteriuria: 1) Asymptomatic Bacteriuria – Updated in 2019 2) Uncomplicated Cystitis and Pyelonephritis – The 2011 version is being updated now. 3) Cather-Associated UTIs – 2010 https://www.idsociety.org/practice-guideline/practice-guidelines/#/+/0/date_na_dt/desc/?organSystem_na_str=Genitourinary The IDSA also discusses ESBL-producing Enterobacterales and their treatment in UTIs in their 2023 Guidelines on Antimicrobial Resistance Gram-Negative Infections https://www.idsociety.org/practice-guideline/amr-guidance/ https://www.idsociety.org/practice-guideline/amr-guidance/