CHALLENGING UTI S: PRIMARY CARE MANAGEMENT

CHALLENGING UTI S: PRIMARY CARE MANAGEMENT Wendy L. Wright, MS, RN, APRN, FNP, FAANP Adult/Family Nurse Practitioner Owner Wright & Associates Family Healthcare, PLLC @ Amherst and @ Concord, NH Partner Partners in Healthcare Education, LLC 1 Objectives Upon completion of this lecture, the participant will be able to: Discuss the various pathogens causing complicated UTIs Identify the treatment (pharmacologic and otherwise) algorithms for individuals with complicated UTIs Discuss the impact of antimicrobial resistance on the treatment of complicated UTIs 2 Urinary Tract Infections Most frequently occurring bacterial infection In the US, 8 million visits yearly for UTI s Up to 100,000 hospitalizations Approximately 15% of all antibiotic prescriptions are for UTI s 40% - 50% lifetime prevalence in women Griebling TL. Urinary tract infection in women. In: Litwin MS, Saigal CS, eds. Urologic Diseases in America. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, D.C.: GPO; 2007. NIH publication 07 5512:587 619 3 1

Urinary Tract Infections: Statistics 25-35% of young, sexually active women will have at least one UTI per year Although environmental factors play a role (I.e. failure to void after intercourse), genetics also plays a role First-degree relatives of women with recurrent infection have an increased frequency of UTI s even when there is no anatomical abnormality Believed to be an alteration in the bacteria aggregation sites in the bladder and urethra Griebling TL. Urinary tract infection in women. In: Litwin MS, Saigal CS, eds. Urologic Diseases in America. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, Wright, D.C.: 2014GPO; 2007. NIH publication 07 5512:587 619 4 Genetic Predisposition Robust fucosyltransferase activity discourages bacterial adherence within the bladder Also, presence of few bacterial adhesion receptor sites is also thought to be protective Women who have a lot of receptor sites or minimal fucosyltransferase activity tend to have more UTI s particularly from E. Coli and have less lactobacilli in the periurethral region again, making a UTI more likely 5 Pathogenesis Urinary tract is normally sterile Intercourse is often responsible; with increased risk in those who void infrequently Bacterial colonization of the perirectal/vaginal area Bacteria are able to ascend through urethra into bladder Asymptomatic bacterial colonization of bladder Increase in infection rates during pregnancy 6 2

Urinary Tract Infections Lower: Cystitis Asymptomatic bacteriuria (ASB) Upper Pyelonephritis (with or without bacteremia) 7 Two Types Two Additional Classifications Uncomplicated Bladder infection or cystitis Complicated Occurs in individuals with structural abnormalities May be asymptomatic or symptomatic May involve the kidneys 8 Consensus Regarding Definition Unfortunately, no true consensus exists regarding a definition but generally thought to be a UTI which occurs in someone at higher risk for an adverse outcomes 9 3

Complicated UTI Definition Infection of the lower or upper urinary tract Presence of a metabolic abnormality, anatomic abnormality, functional abnormality or the presence of a urinary catheter At much greater risk for sepsis or bacteremia http://emedicine.medscape.com/article/203 9975-overview accessed 05-01-2014 10 Complicated UTIs: Predisposing Factors Multiple pregnancies Benign prostate hyperplasia (BPH) Prostate cancer Neurogenic bladder Immunocompromised states Underlying diseases Indwelling catheters http://emedicine.medscape.com/article/203 9975-overview accessed 05-01-2014 11 Risk Factors for Complicated UTI Structural abnormalities BPH Renal calculi and obstruction Catheter Stent Neurogenic Bladder Metabolic or Hormonal Influences Diabetes Pregnancy http://emedicine.medscape.com/article/203 9975-overview accessed 05-01-2014 12 4

Risk Factors Immunodeficiency Transplant recipients Neutropenia HIV disease Recent antibiotic usage Recent surgical procedure Hospitalized patients http://emedicine.medscape.com/article/203 9975-overview accessed 05-01-2014 13 Risk Factors Age and Gender Male gender Pediatric Advanced age Pregnancy 14 Not all are Risk Factors are Created Equal Structural abnormalities Often most difficult to treat Neurogenic bladder, cystocele, rectocele Frequently relapse May require surgical intervention Metabolic and Immune-Modulated Easier to treat Less likely to recur 15 5

Symptoms of Complicated UTI Highly variable May vary from fever only to a myriad of symptoms Dysuria Suprapubic pain Urinary frequency and urgency Foul smelling urine Flank pain Fever and chills Rigors Orthostasis 16 Fever Sepsis Falls Additional Signs and Symptoms: Younger and Older Patient Mental status change Increased or new urinary incontinence Hematuria Anorexia Vomiting 17 Acute Uncomplicated Cystitis: Pathogens Gorbach et al, 1999 Guidelines for Infections in Primary Care 18 6

Complicated UTI: Pathogens Complicated UTI S epidermidis 15% E coli 32% Pseudomonas 20% Enterococci 22% E coli Proteus Klebsiella Enterococci Pseudomonas Mixed Other S epidermidis http://emedicine.medscape.com/article/203 9975-overview accessed 05-01-2014 19 Pathogens: A Discussion E. Coli: Most common cause of both uncomplicated and complicated UTI s Enterococci: Most common gram positive cause of UTI Often associated with recent antibiotic therapy Consider recent urologic procedure Often cause in the patient with an obstructive pathology http://emediciine.medscape.com/article/245559-overview accessed 03-11-2012 20 Pathogens: A Discussion Staphylococcus saphrophyticus Gram positive organism Second most common cause in sexually active woman Pseudomonas Often seen in the individual with an obstructive pathology http://emediciine.medscape.com/article/245559-overview accessed 03-11-2012 21 7

cuti Pathogens Proteus and Klebsiella Predispose the patient to stone formation and are more often than not seen in patients with calculi Tend to be polymicrobial in the setting of an indwelling catheter or stent placement Kasper, D.L. (2005). Harrison s Manual of Medicine (16 th ed.). New York, NY.: McGraw-Hill Companies, Inc. 22 Step Approach to Bacteriuria Patient symptomatic NO YES Complicating Factors? NO Recurrent Symptoms? NO YES YES NO Complicated UTI Asymptomatic bacteriuria Recurrent UTI Upper Tract Symptoms? YES Pyelonephritis Uncomplicated cystitis Adapted Wright, from 2014 Orenstein R et. al. Am Fam Phys. 1999:59:1225-1234. 23 cuti: Diagnosis History Symptomatic Asymptomatic Physical Examination Assess for CVA tenderness Consider STI Consider Urologic abnormality 24 8

cuti: Diagnosis Urinalysis Macro or microscopic hematuria Alkaline ph Present with urea splitting bacteria (Proteus) > 10 wbc/hpf Positive result on leukocyte dipstick correlates well with > 10 wbc/hpf + Nitrite dipstick for bacteriuria High rate of false negatives WBC Casts suggests upper UTI 25 Important Reminders Odor: Rancid or ammonia odor suggests urea-splitting organism (Proteus) Leukocyte esterase May not be present in a neutropenic patient Nitrites Should be conducted on 1 st morning urine Or no void x 1 hour (takes 1 hour for nitrate to nitrite conversion to occur) May be negative in early infection or gram positive organism 26 ph 5 6: average 4.5-5.5: acid ph 6.5-8: alkaline ph Important Reminders If alkaline ph: consider urea splitting organism such as Proteus Proteus allows urea to be split into CO2 and ammonia which causes a rise in urine s ph http://emediciine.medscape.com/article/245559-overview accessed 03-11-2012 27 9

cuti: Diagnosis Urine culture and sensitivity required Pregnancy test May need additional imaging 28 Additional Diagnostic Options Ultrasound of kidney Polycystic kidneys Atrophic kidney CT scan or IVP if kidney stones suspected Ultrasound of bladder Assess for post-void residual VCUG Assess for vesicoureteral reflux http://emediciine.medscape.com/article/245559-overview accessed 03-11-2012 29 Voiding Cystourethrogram http://emediciine.medscape.com/article/245559-overview accessed 03-11-2012 30 10

Treatment of Complicated UTIs Decision for treatment should be based upon local resistance patterns, patient population, duration of therapy, cost and side effects Resistance patterns vary depending upon geographic locations Highest resistance patterns: West Coast 31 Gram Negative Surveillance: TRUST II (2006 2007): % susceptible Bacteria LVX CIP AMP CRO CAZ IPM PTZ GEN SXT E Coli 80.5 79.9 51.1 96.1 96.7 100 95.5 91.4 73.7 Proteus 78.4 72.6 80.6 99.7 99.7 100 100 90.5 74.8 Klebsiella 93.3 92.2 4.3 95.8 95.7 99.8 94.4 95.5 89.9 Pseudom. 68.8 70.8 0 22.6 86.7 82.6 89.8 87.8 13.6 S marcesc 96.0 94.4 13.6 96.0 96.6 99.4 98.1 96.9 97.5 Citrobacter 95.3 93.4 28.4 91.9 90.2 100 91.9 94.5 86.7 E. Cloacae 88.3 86.4 12.8 75.5 73.8 100 80 90.9 83 LVX = levofloxacin; CIP=ciprofloxacin; AMP = ampicillin; CRO=ceftriaxone; CAZ=ceftazidime; IMP=imipenem; PTZ=piperacillin-taxo; GEN=gentamicin SXT=TMP/SMX 32 Susceptibility of Key Uropathogens Uropathogen Antimicrobial Susceptibility In vitro activity does not necessarily imply a correlation with clinical effectiveness TSN Database-USA. MRL Pharmaceutical Services. 1996. 33 11

Complicated UTI: Antimicrobial Choices Trimethoprim-sulfamethoxazole (TMP-SMX) Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) Aminoglycosides (gentamicin, tobramycin, amikacin) Third-generation cephalosporins (ceftriaxone) 34 Mild Moderate cuti Guidelines pertain if patient is not residing in long-term care facility or recently received fluoroquinolones Levofloxacin 250 mg - 500 mg orally once daily Ciprofloxacin 250 mg - 500 mg two times daily or 1000 mg XR once daily 35 Dosage Adjustment Must make sure to account for CrCl in older population May need to reduce dosage based upon level of kidney disease 36 12

Culture and Sensitivity Once C&S has returned, may narrow spectrum of antibiotic Consider blood cultures Consider CBC Consider hospitalization, based upon presentation 37 Guidelines for Treatment Severely ill, recent FQ or long-term care facility resident Imipenem Piperacillin-tazobactam Tobramycin or Gentamycin 38 Nosocomial UTI s Up to 40 45% of nosocomial infections are UTI s Usually the result of instrumentation or indwelling catheter 3 10% risk of infection for every day the catheter remains in place Kasper, D.L. (2005). Harrison s Manual of Medicine (16 th ed.). New York, NY.: McGraw-Hill Companies, Inc. 39 13

Symptoms: Nosocomial Infections Most frequently will see upper urinary tract symptoms Flank pain, fever, chills, rigors, leukocytosis Lower tract symptoms are often not present Dysuria Kasper, D.L. (2005). Harrison s Manual of Medicine (16 th ed.). New York, NY.: McGraw-Hill Companies, Inc. 40 Treatment If possible, remove catheter Consider condom catheter in men Antimicrobial therapies (dosages for elderly lower) AMP+gentamycin PIP-TZ IMP Ciprofloxacin or Levofloxacin IV Length of treatment 14 21 days Switch to oral antimicrobial when clinically stable 41 Recurrent UTIs Definition 3 or more episodes per year or 2 or more in 6 months Young woman Treatment Eradicate infection TMP SMX single strength 1 daily x 3 6 months Additional option TMP-SMX DS two tabs at onset of symptoms or TMP- SMX DS 1 post-coital Nitrofurantoin 50 mg at bedtime or post-coital Cephalexin 250 mg at bedtime or post-coital 42 14

Pyelonephritis Infection of the upper urinary tract, involving renal parenchyma and renal pelvis Potentially organ and life-threatening infection which results in kidney scarring and may lead to significant renal damage Kidney failure Abscess formation (nephric and perinephric) Sepsis Multiorgan failure 43 Pyelonephritis Annual rates: 15 17 cases per 10,000 females 3-4 cases per 10,000 males 250,000 cases per year 200,000 require hospitalization 44 Pathogens Most common pathogen continues to be E. Coli Cause of > 90% of pyelonephritis cases Suspect and target E. Coli in the individual with no stones/calculi and mild illness 45 15

Other Pathogens Klebsiella pneumoniae Proteus mirabilis Enterococci Staphylococcus aureus Psuedomonas aeruginosa Enterobacter species 46 Symptoms of Pyelonephritis Not always straightforward High variability May be associated with fever, flank pain Dysuria, urinary urgency and frequency Nausea, vomiting, bacteremia Symptoms often begin and advance rapidly 47 Diagnosis made: Pyelonephritis History and physical examination Urine microscopy Culture and sensitivity Blood cultures are now recommended before antibiotic initiation 48 16

Pyelonephritis Treatment Options For patient s deemed suitable for outpatient treatment: Obtain urinalysis Obtain blood cultures Antimicrobial therapies Fluoroquinolone (preferred agent) Trimethoprim/sulfamethoxazole (alternative) 49 Mild / Moderate Pyelonephritis Fluoroquinolone x 7-14 days Ciprofloxacin 500 mg 1 po two times daily or ciprofloxacin ER 1000 mg 1 po daily Ofloxacin 400 mg 1 po two times daily Levofloxacin 250 mg once daily Other secondary options TMP/ SMX DS 1 po bid x 10 14 days AM-CL: 875/125 mg po every 12 hours Consider calculi if the individual relapses after treatment 50 Importance of Rapid Assessment and Treatment During an acute pyelonephritis, there is a significant and rapid reduction in the perfusion of the kidney Subsequent renal tubular dysfunction and scarring is possible if not treated aggressively and rapidly Always suspect pyelonephritis in any patient with UTI symptoms 51 17

Caution Children should undergo comprehensive workup after first episode of pyelonephritis as there is frequently an anatomic abnormality Usually, vesicoureteral reflux Renal scarring can be detected in 6 15% of children after a febrile UTI 52 Pathogens E. Coli (>90%) Enterococci Klebsiella Proteus Severe Pyelonephritis IV antibiotic is recommended (total treatment: 14 days) Hospitalization with blood cultures and septic work-up is essential 53 Antimicrobial Treatment: Severe Pyelonephritis Third generation cephalosporins Cefotaxime 1 gram IV every 12 hours; 2 grams IV for lifethreatening cases Ceftriaxone 1 2 grams IV every 24 hours Use 2 grams in individual < 65 years of age Second generation fluoroquinolones Ciprofloxacin 400 mg IV every 12 hours Levofloxacin 250 mg every 24 hours Ampicillin + gentamicin 54 18

Severe Pyelonephritis Treatment Step down to oral therapy 24-48 hours after patient becomes afebrile If no improvement in 72 hours, obtain CT of kidneys Imaging is indicated earlier in the patient with suggestions of obstruction or lifethreatening illness (i.e. abscess) 55 Acute Pyelonephritis and Diabetes Perinephric abscess formation can occur Papillary necrosis is a more common consequence of AP in patients with diabetes Infection of the renal pyramids Acute renal failure with oliguria or anuria can occur Unfortunately, patients with diabetes are more prone to asymptomatic bacteriuria and pyelonephritis Kasper, D.L. (2005). Harrison s Manual of Medicine (16 th ed.). New York, NY.: McGraw-Hill Companies, Inc. 56 Male UTIs UTI s in men < 50 years of age are rare Consideration for the presence of STI s or prostatic abnormality Obtain pretreatment urinalysis, culture and sensitivity. May need GC and chlamydia cultures depending upon risk factors. In general, treatment should be continued for a minimum of 10 14 days 57 19

Epididymitis Symptoms Dysuria Fever Painful swelling of epididymis and scrotum Often unilateral pain and discomfort Most common pathogens Men < 35 years N. gonorrhoeae and C. trachomatis Men > 35 years or MSM (insertive partner) E. Coli 58 Differential Diagnosis Testicular torsion must be considered Time is very important in the individual with torsion Loss of cremasteric reflex No fever Doppler flow study/us of testicle Stat urology consult 59 Treatment Options Men < 35 years of age Ceftriaxone 250 mg IM as a single dose plus Doxycycline 100 mg BID X 10 days Scrotal elevation Bedrest Analgesics 60 20

Treatment Options Men > 35 years of age ciprofloxacin 500 mg QD 10 14 days or levofloxacin 750 mg QD X 10-1 4 days or IV ampicillin with sulbactam or IV 3 rd generation cephalosporin 61 Acute Prostatitis Symptoms Fever, chills, dysuria Tender, boggy prostate Malaise, myalgias and flu-like symptoms Most common in men > 50 years of age or those with indwelling catheter Kasper, D.L. (2005). Harrison s Manual of Medicine (16 th ed.). New York, NY.: McGraw-Hill Companies, Inc. 62 Pathogens: Acute Prostatitis Men < 35 years of age N. gonorrhoeae and C. trachomatis Men > 35 years of age E. Coli 63 21

Treatment: Acute Prostatitis Men < 35 years of age Ceftriaxone 250 mg IM as a single dose plus Doxycycline 100 mg BID X 10 days Avoid fluoroquinolones due to increased antimicrobial resistance 64 Treatment Options Men > 35 years of age Ciprofloxacin 500 mg QD 10 14 days or Levofloxacin 750 mg QD X 10-1 4 days or TMP-SMX 1 DS tablet po bid x 10 14 days 65 Chronic Bacterial Prostatitis Uncommon condition More common in middle aged-older men Most common symptoms: Relapsing UTIs but without symptoms in between episodes Urinary symptoms are often vague Often has history of an acute prostatitis Prostate often feels normal Lacks acuity of acute prostatitis Kasper, D.L. (2005). Harrison s Manual of Medicine (16 th ed.). New York, NY.: McGraw-Hill Companies, Inc. 66 22

Chronic Prostatitis Pathogens E. Coli (80%) Enterococci (15%) P. aeruginosa Treatment options Ciprofloxacin 500 mg bid x 4 weeks Levofloxacin 750 mg daily x 4 weeks TMP SMX DS 1 po bid x 1 3 months If no improvement, consider prostatic calculi Relapsing symptoms are common 67 Asymptomatic Bacteriuria Does not need to be treated routinely Exceptions to this rule may be: Pregnant women Children Patient s who are s/p renal transplant Neutropenic patients 68 Pregnant Women Screen for UTI and asymptomatic bacteriuria in pregnant women Treatment is usually for 7 days Amoxicillin, nitrofurantoin, TMP-SMX, cephalosporin (2 nd or 3 rd generation) Once positive, recommended to screen monthly through pregnancy 69 23

Increased water Frequent voiding Prevention Consider topical estrogen Cranberry tablets Prevent constipation Pre and post-coital voiding Surgical correction of predisposing factors Urodynamic physical therapy http://emediciine.medscape.com/article/245559-overview accessed 03-11-2012 70 Thank You! I Would Be Happy to Entertain any Comments or Questions 71 Wendy L. Wright, APRN Email: WendyARNP@aol.com www.4healtheducation.com 72 24