URINARY TRACT INFECTIONS Learning Objectives Identify signs and symptoms that may indicate presence of UTI (both complicated and uncomplicated) List common causative organisms and risk factors for UTIs Distinguish between antibacterial treatments for UTIs, the organisms they cover, and the monitoring of these regimens Describe the differences in treatment between upper and lower UTIs, as well as recurrent UTIs Background Uncomplicated: an infection in an otherwise healthy, premenopausal female of childbearing age (15-45) who lacks structural or functional abnormalities of the urinary tract Males generally are not classified as uncomplicated because infection in males is rare and often represent a structural/neurologic abnormality Complicated: associated with a predisposing lesion of urinary tract - may also be used to refer to any infection that is not in an otherwise healthy, premenopausal adult female Recurrent infection: either a reinfection or a relapse Reinfection - occurs more than 2 weeks after the last UTI and treated as a new uncomplicated UTI Relapse - within 2 weeks of original infection, due to unsuccessful treatment of original infection, a resistant organism, or anatomical abnormalities Cystitis: lower urinary tract infection that involves the bladder Pyelonephritis: upper urinary tract infections that involve the kidneys Case Example: SR is a 26-year-old woman who presents to a family practice clinic in Seattle with complaints of dysuria, urinary frequency and urgency, and suprapubic tenderness for the past 2 days. PMH Patient has been diagnosed with three UTIs over the past 8 months based on symptoms, each treated with oral TMP SMX SH Denies smoking but admits to occasional marijuana use and social EtOH use. Patient has been sexually active with one partner for the past 9 months and typically uses spermicidecoated condoms for contraception. Home Meds None Looking at the pathophysiology section below, how can this UTI presentation be described (i.e. uncomplicated vs uncomplicated, cystitis vs pyelonephritis, recurrent?)? If this were a male patient, how would this change the evaluation?
Pathophysiology Bacteria that cause UTIs usually originate from bowel flora of host The short length of the female urethra and its proximity to the perirectal area make colonization of urethra more likely Sexual intercourse allows bacteria to reach bladder Once here, organisms quickly multiply and can ascend to kidneys After bacteria reach the urinary tract, three factors determine the development of infection: the size of the inoculum the virulence of the microorganism the competency of the natural host defense mechanisms Host defense mechanisms Low ph, extremes in osmolality, high urea concentrations, and high organic acid concentration all fight infection normally Additionally, introduced bacteria into bladder stimulates increased diuresis and efficient emptying of bladder Patients unable to void urging completely at increased risk of UTI (frequently experience recurrent infections) Circulating estrogen in premenopausal women supports vaginal tract growth of lactobacilli, which produce lactic acid to help maintain a low vaginal ph Prevents E. coli colonization Bacterial virulence factors The mechanism of adhesion of gram-negative bacteria, particularly E. coli, is related to bacterial fimbriae that are rigid, hair-like appendages of the cell wall Risk factors: Females more likely to become infected than males due to anatomical differences Obstruction can inhibit normal flow of urine and disrupt natural flushing and voiding, reducing removal of bacteria from bladder Urinary catheterization Mechanical instrumentation Pregnancy Use of spermicides and diaphragms (females) Common conditions that result in residual urine volumes include prostatic hypertrophy, urethral strictures, calculi, tumors, bladder diverticula, and drugs such as anticholinergic agents. Additional causes of incomplete bladder emptying include neurologic malfunctions associated with stroke, diabetes, spinal cord injuries, tabes dorsalis, and other neuropathies Signs/Symptoms General VS BP 110/60, P 68, RR 16, T 36.8 C; Wt 57 kg, Ht 5 5
Signs and Symptoms Urethral pain and burning with urination, as well as mild suprapubic tenderness. Pt denies systemic symptoms (fever, chills, vomiting, or back pain) and does not report any urethral or vaginal discharge. Upon further questioning, the patient notes that the UTIs started soon after she met her boyfriend, and she does not always completely empty her bladder after sexual intercourse. Laboratory Tests Urinalysis Yellow, cloudy; ph 5.0; WBC 50 cells/hpf; RBC 1 5 cells/hpf; protein neg; trace blood; glucose ( ); leukocyte esterase (+); nitrite positive; many bacteria Does this additional information help you confirm your conclusions above? Would you change your assessment with any of this new information? What are the most common causative pathogens of acute uncomplicated cystitis in females? ASB = asymptomatic bacteriuria Common finding, especially 65+ years NOT recommended to treat in IDSA guidelines Treating asymptomatic bacteriuria has been shown to be more harmful than beneficial in patients - a common misperception among healthcare providers Dysuria: painful urination Gross hematuria (blood in urine) Systemic symptoms (i.e. fever) often absent Lower UTI: dysuria, urgency, frequency, nocturna, suprapubic heaviness Upper UTI: flank pain, fever, nausea, vomiting, and malaise Elderly patients often do NOT experience urinary symptoms Altered mental status Change in eating habits GI symptoms Patients with indwelling catheters or neurologic disorders commonly do not have lower tract symptoms Present with flank pain and fever Symptoms alone = unreliable for diagnosis Key is to demonstrate significant numbers of microorganisms in appropriate urine specimen See diagnostic section
Testing/Diagnostics Urine collection The diagnosis of UTI is based on the isolation of significant numbers of bacteria from a urine specimen The presence of pyuria in a symptomatic patient correlates with significant bacteriuria. Pyuria WBC count of greater than 10 WBC/mm 3 (10 10 6 /L) of urine Pyuria is nonspecific and signifies only the presence of inflammation and not necessarily infection Patients with infection usually have greater than 10 5 bacteria/ml (10 8 /L) of urine As many as one-third of women with symptomatic infection have less than 10 5 bacteria/ml (10 8 /L) A significant portion of patients with UTIs, either symptomatic or asymptomatic, have less than 10 5 bacteria/ml (10 8 /L) of urine Hematuria or proteinuria may be other indicators of infection Urinalysis Pharmacist should look at 4 things to help determine UTI from a UA: WBC: significant when > 100 in the urine Leukocyte esterases Precursor to WBC, presence indicative of infection Nitrite Breakdown of bacteria Nitrites + bacteria in urine indicative of gram negative infection Bacteria but no nitrites indicative of gram positive or Proteus infection Bacteria: positive vs negative Causal Organisms Virtually every organism associated with UTIs Organisms seen with uncomplicated UTIs: E. coli (80-90%) Staphylococcus saprophyticus, Klebsiella pneumoniae, Proteus spp., Pseudomonas aeruginosa, and Enterococcus spp Complicated infections causative organisms are more varied and generally are more resistant: E. coli (less than 50%) Proteus spp., K. pneumoniae, Enterobacter spp., P. aeruginosa, staphylococci, and enterococci Vancomycin-resistant E. faecalis and E. faecium have become more prevalent
Most UTIs are caused by a single organism; however, in patients with stones, indwelling urinary catheters, or chronic renal abscesses, multiple organisms may be isolated Treatment Options Considerations for treatment: Does the patient have a catheter? Is the patient pregnant? Treat even asymptomatic bacteriuria Patient allergies and recent antibiotic use The initial selection of an antimicrobial agent for the treatment of UTI is primarily based on the severity of the presenting signs and symptoms, the site of infection, and whether the infection is determined to be complicated or uncomplicated.
Outpatient treatment - note durations differing of therapy!!
Inpatient treatment
Treatment for Our Case: What are the therapeutic goals in the treatment of acute uncomplicated cystitis? What drug, dosage form, dose, schedule, and duration of therapy are best for the treatment of this patient s acute uncomplicated cystitis? What long-term treatment strategies could be employed for this patient with recurrent acute uncomplicated cystitis? How should this patient be managed if she presents with continuing symptoms of a UTI 3 days after finishing the antibiotic treatment originally prescribed? If this patient were pregnant, what antibiotics would be appropriate for treatment? Review the safety and efficacy of single-dose, 3-, 5-, and 7-day antimicrobial therapy for the treatment of acute uncomplicated cystitis. Monitoring Caution with recurrent infections! While UTI regimens are generally short, recurrence can be an issue with some patients Some symptoms are nonspecific, be sure patient truly warrants antibacterial therapy Renal function important with pyelonephritis Drug specific monitoring important - see Drug-Bug Sheet for this References Link to guidelines: https://academic.oup.com/cid/article/52/5/e103/388285 Link to DiPiro Handbook: https://accesspharmacy-mhmedicalcom.pitt.idm.oclc.org/content.aspx?bookid=2177§ionid=165473379#1144735409 Great tables for the differing types of UTI Link to DiPiro Chapter 116: https://accesspharmacy-mhmedicalcom.pitt.idm.oclc.org/content.aspx?bookid=1861§ionid=146072433#1145824614