Introduction UTIs represent a wide variety of syndromes including urethritis, cystitis, prostatitis, and pyelonephritis. One of the most commonly occurring infections. Introduction Young women are particularly susceptible, 40% of all women will suffer at least one UTI at some point. Infection in men occurs less frequently until the age of 50, when incidence in men and women is similar. Definition It is the presence of microorganisms in the urinary tract that cannot be accounted for by contamination. The organisms have the potential to invade the tissues of the UT and adjacent structures. Definition A UTI can manifest as several syndromes associated with an inflammatory response to microbial invasion that range from asymptomatic bacteriuria to pyelonephritis. Classification According to anatomic site of involvement: Lower tract infection: cystitis, urethritis, prostatitis Upper tract infection: pyelonephritis, involving the kidneys Classification According to Degree 1-Uncomplicated Occur in individuals who lack structural or functional abnormalities in the UT that interfere with the normal flow of urine. Mostly in healthy females of childbearing age Classification According to Degree 2-Complicated predisposing lesion of the UT such as congenital abnormality or distortion of the UT, a stone a catheter, prostatic hypertrophy, obstruction, or neurological deficit All can interfere with the normal flow of urine and urinary tract defenses. Recurrent UTIs Multiple symptomatic infections with asymptomatic periods Reinfection: caused by a different organism than originally isolated and account for the majority of recurrent UTIs. Relapse: repeated infections with the same initial organism and usually indicate a persistent infectious source. Other Definitions Asymptomatic bacteriuria Common among the elderly Bacteiruria > 105 bacteria/ml of urine without symptoms Symptomatic abacteriuria: Symptoms of frequency and dysuria in the absence of significant bacteriuria Other Definitions Significant bacteriuria More than 105 bacteria /ml (CFU) of urine in clean catch specimen 1/3 of symptomatic women have CFU counts below this level A bacterial count of 100 CFU/ml has a high positive predictive value of cystitis in symptomatic women Other Definitions
Count less than 105 may represent
true infection in certain situations Concurrent antibacterial drug administration Rapid urine flow Low urine PH Upper tract obstruction Etiology The microorganism that cause UTIs usually originate from the bowel flora of the host Uncomplicated UTI: E.coli accounts for 85% S.saprophyticus 5-15% K.pneumoniae, protues sp, Pseudomonas, and Enterococcus 5- 10% S.epidermidis if isolated should be considered a contamination Etiology Complicated UTIs More varied and generally more resistant E.coli 50% K.pneumoniae, protues sp, Pseudomonas, Enterococcus, Enterobactor sp Etiology Complicated UTIs Enterococcus fecalis 2nd most frequently isolated organism in hospitalized patients S.aureus infection is more commonly a result of bacteremia producing metastatic abscesses in the kidney Candida sp is common cause of UTI in critically ill and chronically catheterized patients Etiology The majority of UTIs are caused by a single organism In patients with stones , indwelling catheter, or chronic renal abscesses multiple organisms may be isolated Although this may be due to contamination and a repeat evaluation should be done. Predisposing factors Abnormalities in the UT that interfere with natural defenses 1-Obstruction can inhibit urine flow, disrupting the natural flushing and voiding effect in removing bacteria from the bladder and resulting in incomplete emptying Predisposing factors Abnormalities in the UT that interfere with natural defenses. 2-Condition that result in residual urine volumes e.g. prostatic hypertrophy, urethral stricture, calculi, tumors, and drug such as anticholinergic agents, neurological malfunctions associated with stroke, diabetes, and spinal cord injuries. Predisposing factors Abnormalities in the UT that interfere with natural defenses. 3-Other risk factors include: urinary catheter, mechanical instrumentation, pregnancy, and the use of spermicidies and diaphragms Clinical presentations Lower tract infection: Include dysuria, urgency, frequency, nocturia, suprapubic heaviness, and hematuria in women. No systemic symptoms Upper tract infection: Flank pain, costovertebral tenderness, abdominal pain, fever, nausea, vomiting and malaise. Clinical presentations Elderly patients: Frequently do experience specific urinary symptoms Altered mental status, change sin eating habits, or GI symptoms Patients with catheters Will have no lower tract symptoms Just flank pain and fever Laboratory findings Symptoms alone are unreliable for diagnosis Examination of the urine is the cornerstone of diagnosis Collection of urine: Mid stream clean catch method is preferred method Laboratory findings Collection of urine: Catheterization for patient who are uncooperative or unable to void, but introduction of bacteria in the bladder occurs at 1-2% Suprapubic aspiration bypasses the contaminating organism in the urethra, safe and painless. Diagnosis: Based on isolation of significant numbers of bacteria from a urine specimen Microscopic examination is performed by preparing a gram stain that indicates the morphology of the organism and help direct the selection of an appropriate AB. Diagnosis: Microscopic examination The presence of one organism per oil-immersion field in an un centrifuged sample correlates with 100,000 bacteria/ml Diagnosis: Pyuria: WBC > 10 WBC/mm3 it only signifies the presence of inflammation Sterile pyuria is associated with urinary tuberculosis, chlamydial, and fungal infections Diagnosis:
Hematuria, non-specific, may indicate
other disorders such as calculi or tumor Protenuria is found in the presence of infection Diagnosis Biochemical tests 1-dipstick test for nitrite: bacteria in the urine reduce nitrate nitrite false negatives are common and caused by gm+ve or pseudomonas that do not reduce low urinary PH frequent voiding and dilute urine Diagnosis Biochemical tests 2- leukocyte esterase dipstick test rapid screening test for detecting the presence of pyuria LE is found in neutrophills Specific for detecting more than 10 WBC/mm3 Diagnosis Quantitative urine culture Based on properly collected urine Urine is normally sterile Determines the number of bacteria present in a urine sample 1/3 of symptomatic women have bacteria < 105 Diagnosis Quantitative urine culture one organism per oil immersion field correlates with 100,000 CFU/ml by culture Susceptibility determine bacterial susceptibility to different antimicrobials Treatment Desired outcome Prevent or treat systemic consequences of infection Eradicate the invading organism Prevent reoccurrence of infection Treatment Non-specific therapies 1-fluid hydration: rapid dilution of bacteria and removal of infection through increased voiding 2-cranberry juice increase the antibacterial activity of urine Treatment Non-specific therapies 3-urinary analgesics phenazopyridine has little clinical role in infection because symptoms respond rapidly to anitmicrobial therapy Acute uncomplicated cystitis Most common form of UTI? Occur in women of childbearing age Can be explained by sexual activity anatomy (short urethra) delay in micturation use of diaphragm and spermicidal Causes Mostly cause E.coli Other causes : S.saprophyticus. K.pneumonia, Proteus mirabilis Acute uncomplicated cystitis Management: Urinanalysis including microscopic examination, cell count, and LE test C&S add little to the choice of therapy empiric therapy Regarding the use of laboratory tests to diagnose urinary tract infections, which of the following statements is correct? A. In a patient with suspected cystitis, urine dipstick results should be confirmed with a urinalysis B. The urine should always be cultured in outpatients with acute cystitis C. Urine dipstick results usually provide the laboratory information needed to manage young otherwise healthy patients with acute cystitis D. The use of urine dipsticks should be avoided; urinalysis is the test of choice. Acute uncomplicated cystitis Management: 1- Single dose therapy 65-100% cure rate with SMX- TMP, amoxicillin advantages of single does: less expensive better compliance low side effects low potential for development of resistance Acute uncomplicated cystitis 1- Single Dose Therapy Not all agents are effective as single dose 2 DS TMP/SMX is most effective Flouroquniolones: 800 mg norfloxacin, 125 mg ciprofloxacin, 200 ofloxacin B-lactam are less effective due to increasing resistance and because they are eliminated rapidly and do not achieve high urine concentrations Acute uncomplicated cystitis 2-Three day course single dose Tx was blamed for high rate of recurrence within six weeks this may be due to failure to eradicate gm-ve bacteria from the rectum TMP/SMX or fluoroquinilones is superior to single dose Amoxicillian, nitrofurantion, and sulfonamides are not appropriate due to increasing resistance of E.coli Acute uncomplicated cystitis Management: Short course therapy is not appropriate for Patient with previous infection with a resistant bacteria Male patients Complicated UTI Acute uncomplicated cystitis Management: If symptoms do not respond or they reoccur, a urine culture should be obtained and conventional therapy started Fluoroqunilones should not be used unless patient cannot tolerate TMP/SMX Theyre a high frequency of resistance due to recent antibiotic use Acute uncomplicated cystitis Management: 3-Seven-day course in pregnant women diabetic women women who have had symptoms for more than one week and are at higher risk for pyelonephritis Symptomatic abacteriuria Acute urethral syndrome In females, present with dysuria and pyuria Urine culture reveals < 105 bacteria /ml Accounts for half the complaints of dysuria in women Most likely infected with a small number of bacteria Symptomatic abacteriuria Causes: E.coli, S. saprophyticus, or chalmydia Other causes: Most patients will require short course therapy as above Symptomatic abacteriuria Chlamydial treatment 1g of azithromycin or doxycycline 100 mg bid for 7 days Concomitant treatment of sexual partner is required to cure this infection and prevent recurrence Asymptomatic bacteriuria Patients with no urinary symptoms Have two consecutive urine cultures with > 105 The majority are elderly and female Asymptomatic bacteriuria Aggressive treatment does not affect infection, complications or mortality Also present in pregnant women Relapse and reinfection are common and chronicity occurs which is difficult to eradicate Asymptomatic bacteriuria Management Groups who benefit from treatment: pregnant women patient with renal transplant Patient who will undergo urinary procedure Asymptomatic bacteriuria Management Depend on age and whether they are pregnant In children: conventional treatment because of greater risk for renal damage In non-pregnant female: controversial Asymptomatic bacteriuria Management In elderly: two groups Persistent bacteriuria: Intermittent bacteriuria Mostly seen as a benign disease and does not warrant treatment Two cultures should be obtained to confirm the presence of bacteria Asymptomatic bacteriuria Management Ambulatory treatment is effective in removing bacteria for 6 months Only 50% remained free of bacteria for 1 year Hospitalized patients: therapy in non-efficacious Case 1 A 24-year-old woman comes to the clinic to discuss recent laboratory results. She went to a local walk-in clinic asking to be screened for a urinary tract infection. She comes to the clinic to review them with you. She is asymptomatic and has no past medical history. She is married and has a 3- year-old boy. Her physical exam is unremarkable. A urinalysis showed 1+ leukocyte esterase; a urine culture revealed >100000 CFU of Escherichia coli. Case 1 Which of the following management strategies is the most appropriate for this patient? A. Explain that even though the urine culture was positive she does not need treatment B. Start oral ciprofloxacin for three days C. Repeat a urine dipstick, and if the presence of pyuria is confirmed start treatment D. Start oral ampicillin for seven days Case 1 The IDSA guidelines recommend screening for and treatment of asymptomatic bacteriuria in only three circumstances: pregnancy, before invasive urologic procedures that are associated with mucosal bleeding, and in women who are found to have catheter-acquired bacteriuria that persists 48 hours after the catheter is removed Complicated UTI Accurate urine culture and susceptibility is necessary to target the pathogen Treatment duration at least 10-14 days Acute pyelonephritis Perform uniranalysis, gram stain, C&S Severely ill patients Should be hospitalized and treated with IV Abs Use broad spectrum directed at bacteremia or sepsis Acute pyelonephritis Empiric therapy: 3rd generation cephalosporin with antipseudomanl activity as ceftazidime, cefoperazone Ampicillian + gentamicin TMP/SMX OR Quionoles B-lactamase inhibitor combination: ampicillian/Sulbactam, ticarcillin/clavunate, Aztreonam or imipenem Acute pyelonephritis If the patient has been hospitalized for > 6 months: Consider P.aeruginosa and enterococci, and multiple organisms Empiric therapy: Ticarcillin/clavunate, Piperacillin/tazobactam Aztreonam or imipenem In combination with AG Acute pyelonephritis Management Fluoroquinolones major advantages is their oral formulation. Use as empiric therapy in this setting may be limited because of resistance rates. Acute pyelonephritis Management ceftazidime, cefepime, piperacillin, piperacillin/tazobactam, and aztreonam. They have reliable activity against many nosocomially acquired gram- negative rods, including P aeruginosa. Acute pyelonephritis Management Carbapenems, imipenem-cilastatin and meropenem. have extremely broad-spectrum coverage and should be reserved for only the most severe forms of nosocomial infections, such as multiresistant pathogens, sepsis syndrome, overwhelming intra-abdominal infections, or septic shock Acute pyelonephritis Effective therapy should stabilize patient within 12-24 hrs Bacterial load should reduce in 48 hrs If the patient fails to respond in 3-4 days further investigation is necessary to Exclude bacterial resistance Exclude obstruction Or other disease process Acute pyelonephritis Oral therapy can be started when the patient is febrile for 24 hrs Oral therapy should be continued for 2 wks Follow-up urine cultures should be obtained 2 wks after end of therapy Acute pyelonephritis Mild cases: can be treated orally as outpatients for at least 2 w ks Gram ve bacilli: TMP/SMX or fluoroquiolones Gram +ve: cocci: consider enterococcus fecalis, DOC Ampicillin Case 2 22 year-old woman without any significant past medical history presents to the emergency room with 2 days of worsening fever, urinary frequency, back pain, nausea and vomiting. She is not able to keep food or liquids down. On physical examination she is febrile and tachycardic. The abdominal exam is normal except for the presence of moderate costovertebral angle tenderness. A blood pregnancy test is negative. A urinalysis is obtained and reveals >50 PMN per high power field and 10-25 red blood cells. Blood cultures are sent to the lab. Case 2 Which of the following management strategies is the most appropriate for this patient? A. Order an ultrasound to confirm your clinical impression, and start intravenous antibiotics if needed B. Admit the patient for administration of intravenous antibiotics, and obtain imaging studies only if the patient does not improve after a few days C. Start intravenous antibiotics, and order abdominal CT scan to rule out complicated pyelonephritis D. Discharge the patient home on an oral fluoroquinolone Infection in males Infection in males are considered complicated Occur in presence of functional or structural abnormalities that disrupt the normal defense mechanism of urinary tract. Infection in males The most common causes are Instrumentation Catheterization Renal and urinary stones In the elderly the most common cause is bladder outlet obstruction due prostatic hypertrophy. Infection in males Treatment Urine culture is needed because causative organism is not easily predictable A urine culture with>100 CFU/ml is best sign of infection If Gm ve is TMP/SMX or FQ Duration therapy should be 10-14 days Infection in males Treatment Parental therapy may be required in Severely ill patients The presence of acute prostatitis (may need 6-12 weeks) Patient who cannot tolerate oral MEDs Repeat a follow up culture 4-6 weeks after treatment Case 3 A 53 year-old man with history of benign prostatic hypertrophy comes to the emergency room complaining of burning with urination and increased urinary frequency. He is afebrile, denies back pain, nausea or vomiting. His past medical history is also significant for hypertension and diabetes. He takes hydrochlorothiazide, enalapril, aspirin, metformin and terazosin. On physical examination his prostate is enlarged, but is not tender. Urine dipstick shows 3+ leukocyte esterase. Case 3 A 53 year-old man with history of benign prostatic hypertrophy comes to the emergency room complaining of burning with urination and increased urinary frequency. He is afebrile, denies back pain, nausea or vomiting. His past medical history is also significant for hypertension and diabetes. He takes hydrochlorothiazide, enalapril, aspirin, metformin and terazosin. On physical examination his prostate is enlarged, but is not tender. Urine dipstick shows 3+ leukocyte esterase. Case 3 Which of the following interventions is the most appropriate for this patient? A. Start ciprofloxacin, and order urine culture B. Start Levofloxacin, and order urine culture only of the patient fails to improve after five days of symptoms. C. Start nitrofurantoin empirically D. Admit the patient for intravenous piperacillin/tazobactam Recurrent infection Reinfections: 80% 0f recurrent infection Infection by an organism different from the initial infection Mostly occurs in females where reinfection rate is 20% Factors contributing to infection: 1-sexual intercourse 2-diaphram and spermicidal use 3- postmenopausal women Recurrent infection Divided into two groups: 1-Those with less than 2 or 3 episodes per year Each episode should be treated as a separate infection Short course therapy is appropriate Can be self administered Recurrent infection Divided into two groups: 2-Those with more than 3 episodes per year Long-term prophylaxis may be needed Patient should be treated conventionally before prophylaxis is started Recurrent infection Regimen: TMP/SMX SS tables OD TMP 100 mg OD Fluroqunilone Nitrofurantion 50-100 mg OD Continued for 6 months Urine cultures followed monthly If symptomatic episodes develop they should be treated with a full course Recurrent infection Infection related to sexual activity: Voiding after intercourse Single-dose prophylactic with TMP/SMX taken after intercourse In postmenopausal women Recurrent episodes related to decreased estrogen and changes in bacterial flora TX: topical estrogen cream Relapses Persistence of the infection with the same organism after therapy Usually indicate structural abnormality, renal involvement, or chronic bacterial prostatitis Relapses In women: If relapse after short course treat with 2 week course In-patient who relapse after 2 wk course continue for another 2-4 wks If relapse after 6 wks of therapy, urologic evaluation and any obstruction corrected May need therapy for 6 months Relapses In males Relapse usually indicate bacterial prostaitis TMP/SMX and fluroquniolones appear to be highly effective for relapses Case 4 A 26-year-old woman comes to the clinic complaining of recurrent cystitis. Over the previous year she has had 5 episodes of cystitis that were treated with antibiotics. The symptoms improved rapidly after each course of therapy. The episodes have happened once every two to three months for the last year. Her past medical history is otherwise unremarkable. She uses oral contraceptives for contraception. She has had two urine cultures done during the previous year that showed pansusceptible Escherichia coli. The patient asks for ways to prevent these infections from coming back. Case 4 Based on the history and test results, which of the following interventions is indicated on this patient? A. Ask the patient to report the onset of infection as soon as possible, and start treatment if a urine dipstick is positive B. Offer antibiotic prophylaxis C. Change her contraception to spermicides and diaphragms D. Obtain abdominal ultrasound to look for a secondary cause of recurrent UTIs E. Perform an immunologic evaluation to rule out an underlying immune deficiency Pregnancy Predisposing factors: Dilation of the renal pelvis and ureters Decrease urethral peristalsis Reduced bladder tone All lead to urine stasis and reduced defenses against reflex of bacteria to the kidney Hormonal changes predispose to infection Pregnancy Asymptomatic bacteriuria Occur in 4-7% 20-40% will develop acute pyelonephritis Routine screening for bacteriuria should be performed at the initial prenatal visit and at 28 wks Pregnancy Significant bacteriuria should be treated regardless of symptoms Organism is the same for uncomplicated UTI Therapy should be for 7 days Pregnancy Regimen Sulfonamide (not in 3rd trimester) amxoicillin augmentin cephalexin nitrofurantion Not TCN, fluoroquinoloes Follow up urine culture 1-2 wk after completing therapy, then monthly until gestation Catheterized patients Most common cause of hospital aquired UTI diagnosis is difficult, patients often have some degree of pyuria Virtually all patients with catheters for 1 to 2 wks exhibit bacteriuria, making differentiation of infection from colonization difficult. often lack symptoms Occur in 5% of patients Catheterized patients Etiology often polymicrobial. Causative agents include P aeruginosa and nosocomial gm ve rods, with more resistant susceptibility profiles; enterococci; and Candida species. Diagnosed with > 100 CFU/ml of urine from catheter Urinalysis and urine cultures should always be obtained. Catheterized patients Management 1-Asymptomatic, Remove the catheter Do not treat unless immunosuppresed patient Patient at risk of endocarditis Patient who will undergo urinary tract instrumentation Catheterized patients Management 2-Symptomatic Remove the catheter and treat as complicated UTI Vancomycin-Resistant Enterococci VRE are often isolated from urine cultures of patients who have been hospitalized for a prolonged period. Most commonly, a urinary catheter is present. If the organism is E.faecalis, then penicillin/ampicillin susceptibility is frequently maintained, and ampicillin is the treatment of choice. VRE However, most VRE are E. faecium that are also resistant to ampicillin (VARE) and to multiple other antimicrobials. Many VARE are susceptible to nitrofurantoin, and it can be used as long as the patient has a CrCL >60 mL/min VRE Chloramphenicol or novobiocin, with or without other drugs, have been used. Two newer antibiotics, quinupristin/dalfopristin and linezolid, have been marketed for gram-positive infections and have activity against VARE. VRE- Quinupristin/dalfopristin The 1st injectable streptogramin antibiotic. It inhibit protein synthesis and has bactericidal effect with the exception of VARE. spectrum is mostly gm+ve and includes Staphylococcus species (both methicillin- susceptible and methicillin-resistant Staphylococcus aureus), E faecium, and VARE. It is not active against other enterococci including E faecalis. VRE- Quinupristin/dalfopristin toxicities chemical phlebitis (especially when infused via a peripheral line) myalgias and arthralgias (particularly in patients with hepatic insufficiency). It is a potent, noncompetitive inhibitor of cytochrome P-450 3A4. significantly increase plasma levels of cyclosporine and long-acting benzodiazepines VRE- Linezolid The first oxazolidinone antibiotic. available as parenteral and oral formulations. It inhibits protein synthesis. It displays a bacteriostatic effect, except with Streptococcus pneumoniae. Its spectrum is broad against gm+ve and includes M-susceptible and MR S aureus, coagulase-negative staphylococci, and many enterococci (including E faecalis, E faecium,). VRE- Linezolid Toxicity Thrombocytopenia that most commonly occurs after prolonged therapy (more than 17 days). Given that linezolid has broader spectrum against the enterococci and is available as an oral formulation, it may be preferred over quinupristin/dalfopristin in the treatment of VARE UTIs. Fungal Infection Many patients with a long-term catheter will have colonization of their bladder with Candida species or, rarely, other fungi. Fungal Infection Usually funguria in the absence of pyuria should not be treated, and the catheter should be removed. Funguria should be treated in renal transplant recipients those undergoing an elective urologic procedure. Fungal Infection Diagnosis pyuria (> 20 WBC/hpf) > 105 fungal organisms / ml of urine. Patients may or may not have systemic findings, such as fever and leukocytosis. Fungal Infection Treatment The catheter should be removed, since this will result in cure in some patients. If C.albicans infection, then oral fluconazole, 100 mg/d, should be prescribed for a 2- to 5-days IV fluconazole should be reserved for patients without the ability to take oral medications or in those with ileus or bowel obstruction. Fungal Infection Treatment Non-albicans Candida species, including C.parapsilosis, C.glabrata, and C.krusei, are becoming more common. The Tx should be either low-dose IV amphotericin B (0.1 mg/kg/d) or continuous amphotericin B bladder irrigation. Both regimens are effective when given for 2 to 5 days.