Microbiology #1 || 14-4-2011 || Dr.

Ziad alNaser || Aseel Alhader & Nomi Almomani

Urinary Tract Infections

The urinary system as you know can be divided into an upper urinary tract (kidneys and ureters) and a lower urinary tract (bladder, urethra and urethral sphincters). Infections to the upper urinary tract usually happen in the kidneys (pyelonephritis), ureters are rarely infected. In the lower urinary tract, most of the infections in the urethra are mainly sexually transmitted (Neisseria gonorrhoeae, Chlamydia, some parasites) Symptoms associated with the upper urinary tract infections are more severe than the ones associated with the lower urinary tract; upper UTI (urinary tract * infections) may present with flank pain and a fever.
*[from the internet] Flank: the posterior portion of the body between the ribs and the ilium. Flank pain is sometimes associated with the kidney.

Some terminologies that are associated with the urinary tract infections: Bacteriuria; the presence of bacteria in the urine, is mainly asymptomatic, and sometimes it could be of significance when you screen for it. Pyelonephritis; infection of the pelvis of the kidney in the upper urinary tract. Cystitis infection of the urinary bladder. And Urethritis infection of the urethra. Prostatitis; infection of the prostate gland, well talk more about it and how we collect the specimen using what we call Void Bladder VB in order to make the diagnosis of prostatitis.

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 Infection to one of these could affect the others; this means that infection at any site of the urinary tract may spread to involve other areas of the system. So wherever the urine takes the bacteria its going to cause infections, the urine usually flows then infection will follow. The flushing action of the urine usually expels pathogens, which is considered as a non-specific immune response, and well be talking about that as part of the treatment of the urinary tract infections; most of the UTIs are going to be cleared out by drinking lots of fluids. Anything that interferes with urine flow can cause a urinary tract infection (such as stones, benign prostatic enlargement). Urine is an excellent media for certain microorganisms to grow, especially if the patient has diabetes, and the pH of the urine is appropriate for many microbes. Urine is completely sterile, when it comes out of the urethra it will be contaminated by the normal flora at the tip of the urethra which comes from the anal orifice, so the bulk of the bacteria that causes infection to the urinary tract comes from the coliform bacteria of the colon; Escherichia coli, Klebsiella, Proteus, Enterobacter; which are members of what we call the Enterobacteriaceae. So urine is sterile, and in the past they used to urinate on wounds or infections in the eye to clean them out. D: Epidemiology: UTIs are more common in females compared to males; 20% of females have a history of UTI, and thats because the urethra is shorter in females (4 cm compared to about 20 cm in males), and also because the urethra is very close part of the vagina so it can be easily contaminated. So they can easily get what is called honeymoon cystitis that is associated with sexual intercourse.

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Around 1% of children could have UTI, and they are mostly associated with congenital abnormalities, reflux of the urine (vesicoureteral reflux), bladder diverticuli, or stasis of the urine, anything that interferes with the flow of the urine is going to cause infections, ureterolithiasis (kidney stones), ureterolithiasis (stones in the ureter) or bladder stones for example. So anybody who has stones will have an infection, this is rule of the thumb because of the interference with the flow of the urine. In the elderly it is mainly because of the enlargement of the prostate benign enlargement of the prostate- which causes interference with the flow of the urine. Delaying the trip to the bathroom is one of the causes of benign enlargement of the prostate which could lead to UTI as well. Instrumentation; if we introduce catheters without following a proper aseptic technique then we could be introducing microorganisms into the urinary bladder and causing infection. Chronic urethral catheterization in almost 10% of them, the longer the catheter is kept the higher is the chance to develop UTI. Pathogenesis: Bacteria could come from the vagina or the urethra going up through the urinary tract. Or it could go down to the kidneys from anywhere in our body by disseminating through the blood and ending up in the kidneys. Of course the first scenario is most common in more than 95% of cases, bacteria enters from below going up. Urine is sterile so it has to be infected from a source. - Ascending bacteria that comes from the anal orifice to the tip of the urethra; thats why women should be washing themselves from the front to the back rather than the other way, so that they wont bring bacteria into the tip of urethra.
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- Honeymoon cystitis and sexual intercourse in ladies. - Catheterization. - Blood stream infection; bacteria disseminate in the blood and end up in the urinary tract. - Nutrition of urine vs. flushing action (flow interruption of urine); these are major competing forces for bacteria that reaches the urinary tract. Nutrition of urine: If somebody is having diabetes for example or nephrotic syndrome (loss of proteins from the kidneys), it could be an excellent nutrition for bacteria. Urine in general shouldnt have any sugar or glucose; protein should be so minimal, and urine should be clear. Flushing action: bacteria could also grow in the urine if the patient has urine stasis; no flow of the urine means there will be no wash of the bacteria. So bacteria should be washed immediately we dont want to give it time for adherence. So flow interruption is the rule of the thumb in UTI.

Members of the Enterobacteriaceae (bacteria present in the colon) cause UTI; the most common is E.coli which is present in more than 90% of cases. Different types of pili (attachment proteins) are associated with UTI; bacteria expressing P pili are most frequently associated with infections in the upper urinary tract and they attach to (gal-gal receptors), whereas bacteria expressing type 1 pili are associated with infections of the lower urinary tract and attach to (D-mannose receptors).

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[A] Shows how the bacteria enter the urinary tract from the anal orifice or the vagina, and the adherence to the receptors through the different types of pili. [B] The clearance of the bacteria in the urinary bladder which is very important. [C] Sometimes they can go up into the ureters and kidneys, and cause pyelonephritis. Also they could disseminate from the kidneys and infect any other organs in the body especially if the patient is immunocompromised. Etiological Agents: Single organism is the rule; so UTI is usually caused by one microorganism, so if you see more than one then the specimen is contaminated, unless the patient is severely immunocompromised, diabetic, on steroids or cytotoxic drugs and so on, then we could have more than one microorganism and in this case we have to support that with clinical presentation, so the patient should show signs and symptoms of UTI.
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 E.coli is the most common organism that causes UTI because of its ability to grow in the appropriate environmental conditions of the urine. pH of the urine can vary from about 5.5 to maybe up to 8, it depends on many factors, but mainly its acidic around 6 and this favors growth of many of the Enterobacteriaceae organisms that has pili as attachment proteins. In the colon we have Pseudomonas aeruginosa that could also contaminate the tip of the urethra; they could ascend and cause UTI in the immunocompromised. It is multi-drug resistant. It could come from the environment also when inserting a catheter. And we have some gram +ve bacteria that originally present in the colon, Enterococci for example (from the Group D Streptococci Enterococcus). Group D streptococci can be divided into enterococcus and non-enterococcus, the difference between the two is that enterococcus can grow in high salt concentration (6.5% salt concentration). Enterococcus includes S.faecalis (from the feces) and S. faecium; these are the most common causing UTI among the gram +ve bacteria. Staphylococcus saprophyticus, a coagulase negative staph that also causes UTI. Yeasts, candida for example can cause UTI in immunocompromised, diabetics, catheterized patients, or people on antibiotics for a long period of time. The source of candida is from the vagina or the colon and abusing antibiotics kills most of the normal flora and favors the growth of yeasts which can cause infection. So when we see candida causing UTI we know definitely that this patient is on antibiotics for a long period of time, severely immunocompromised, diabetic, or is on catheter (the longer the patient is on cath. the higher is the chance). UTI is mainly caused by E.coli until proved otherwise.

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Clinical Manifestations: Clinically UTI is so variable. 50% of people could be asymptomatic and discovered accidently, they could have bacteruria and no symptoms at all especially in the case of benign prostatic enlargement. In infants symptoms are non specific; fever, vomiting and failure to thrive (does not grow properly), also nausea (loss of appetite). Upper urinary tract infection is mainly associated with fever and flank pain. In the lower urinary tract infection (i.e. cystitis): 1. Usually there is no fever, but there are more frequent symptoms like dysuria (painful micturition), frequency (going frequently to the toilet), urgency (urgent need to urinate). 2. It is similar to urethritis of sexually transmitted diseases (gonorrhea, chlamydia) they give the same symptoms but the difference is mainly that in the urethritis the patient is going to have urethral discharge, this is mainly a sexually transmitted symptom and well talk about it later. 3. There is bacteruria, hematuria (RBCs in urine). 4. Pain in the suprapubic area where the urinary bladder is [this area can be used to aspirate urine directly from the urinary bladder]. 5. Fever only when kidneys are involved. So fever is mainly in the upper urinary tract infections, in the lower we rarely see fever unless the infection is so severe.

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Pyelonephritis
Pyelonephritis: infection of the pelvis of the kidneys. Its the most common problem in the upper urinary tract.

Symptoms:
1.Fever and flank pain this is the main problem that we see- it depends on the severity. 2.Rigors, vomiting, diarrhea (non-specific or what we call prodromal symptoms), and tachycardia (because of the fever sometimes). 3.Tenderness over the costovertebral area in the back- so when you just tap on the kidney area the pt. feels pain, this is what we call tenderness, so you elicit the pain; this is a sign, if the pt. tells you he feels pain in this area this is a symptom. 4. Occasionally evidence of septic shock, with gram ve bacteria, they disseminate through the blood they could cause gram-ve sepsis, septic shock and death as a sequel to that.

(20-50)% of pregnant women with pyelonephritis will end up having premature babies. Its so important as part of the antenatal care for pregnant women to do urinalysis and look for UTI.

Note: you know that females because of the estrogen and hormones the urine stays in the urinary bladder for a longer period of time and then they could develop UTI, they are immuncompromized temporarily and they are more susceptible to UTI compared to non-pregnant ladies.

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 Obstruction, neurogenic bladder- pt.s with spinal cord injury the bladder fails to contract so the flow of urine will be affected and the pt. ends up with UTI, Necrosis of the renal papillae, impairment of kidney function, kidney stones anything that will lead to obstruction of the urine and if that is not treated could end up with pyelonephritis and maybe renal failure as a sequel to that.

Prostatitis
-Prostatitis: infection of the prostate gland, you know the significance of prostate gland
on males and secretions make the sperms vital, they provide the alkaline PH to neutralize the low PH of the vagina and so on.

Etiology: its the same etiology, E.coli and gram-ve ones that we have talked
about the same bacteria -. Unless the pt. is having a sexually transmitted disease: N.gonorrheae and other bacteria that could cause prostatitis. -In infection, prostate gland will be enlarged, and you know the prostate gland location and how it could block the flow of urine obstruction infection will follow.

Symptoms: Pain in the lower back- usually radiating pain-,

perirectal and testicles pain (sometimes radiation to the testicles).

-Testing of the prostate enlargement- Direct rectal examination- : we have to go with our finger- and I will teach you how to do that- you go in and palpate the prostate gland usually around 3 cm up of the anal orifice where the prostate gland, if its enlarged and feel that and this is part of your clinical training, I think
you should know how to do that.
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* Acute prostatitis: pain, fever, cystitis, obstruction to the urethra and urinary retention sometimes pt.s cant even urinate and so you have install a catheter to relieve their pain. -Tender, indwelling cath. Note: the capacity of the urinary bladder is 500 ml in females and around 750 ml in males can get to 1 liter-almost-, the urinary bladder can get to umbilicus if there is no relief or drainage of the urine.

* Chronic Prostatitis: Asymptomatic to recurrent cystitis and recurrent bacterurea in men. So cystitis is so frequent related to catheterization and as Isaid instrumentationand some other diseases like diverticulae and so on in the urinary bladder or congenital anomalies, reflux in the ureter for example.

Diagnosis of UTI: We start with urinalysis, first we have to observe the color of the urine visually- it has to be clear, light yellow (it depends on your hydration, the more you are hydrated less concentrated urine its going to be light and vice versa. -So it has to be clear, if its turbid it could be because of: bacteria, sugar or protein, so this gives you an idea about that foul smelling if you have infection, so observation is so important.

And then we do microscopic examination. We look underneath the microscope.

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 You will see in our laboratories we have what we call Dipsticks. You just dip the stick in and the change in color will give you lots information, for example:

1-PH of the urine if its alkaline you have to think of bacteria producing urease
and ammonia.

2- Glucose in the urine if the pt. is diabetic or not. Ive told you before how
physicians used to make a diagnosis of diabetes: they used to taste the urine.

3- It also shows protein: if you have infection protein level will be high.

And then we look for WBCs and RBCs. *WBCs: Normally you can see up to 5 to 7, but if it exceeds 10 and more then you have to think of UTI, polymorphonuclear leukocytes. *RBCs: you shouldnt see any RBC in the urine, if we see that it depends whether they are crenated, old or fresh ones: acute cystitis is mainly associated with hematuria.

And then we look for Casts, the crystals (in the lab youll be seeing many of the crystals) oxalate crystals they look like an enveloped character, phosphatelipid- phosphate they look like the grave, also the cysteine crystal, laboratory technicians know about all these things, tb3n those should indicate metabolic diseases,predisposition to urolithiasis or kidney stones and so on. And also in urinalysis we see what we call casts. Casts: are the cells that will come from the upper urinary tract, mainly in UTI the most important one what we call the WBC casts, i.e. cells usually from the distal

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convoluted tubules that will have WBCs on top.(cells that come from the upper
respiratory tract we call them casts, Hyaline casts, sometimes these are normal finding).

RBC casts: indicate glomerulonephritis so important- when you see in the urinalysis report RBC casts you have to think of glomerulonephritis, acute glomerulonephritis, and we also think of upper infection of the urinary tract.

Bacteria: if you see one bacteria under the microscope indicated UTI, this is equivalent to 105 colony forming unit/ml. After that we take the information from urinalysis and clinical presentation. -Btw: sometimes clinical presentation, urinalysis will be enough to make a diagnosis, but for the treatment we have to isolate the microorganism and we have to do antibiotic susceptibility test.

Specimen Collection--Midstream Clean-Catch: So the specimen that we take for culture we call it the Midstream clean-catch, and you should have instruction for males and instruction for females. The idea here is just to let the urine flow uninterrupted and you catch it in the middle and then you culture that with a calibrated loop, we said that quantitation is important for diagnosis so if you have 105 CFU/ml or more you have UTI, less than that you dont this is contamination from the urethra.

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-Nowadays this formula has been changed a little bit in respect of the number you will get, if you get 105 or more this is definite in a way but if you get less you have to correlate that with the clinical presentation of the pt. if the pt. is having clinical presentation and the number is low then you have to take that in consecration. -So spontaneous micturition (you let the urine flow), when the urine flows it will washout the normal flora at the tip of the urethra and this is what we usually see in less numbers when you culture, clean-voided midstream urine: this is the classical specimen. -For females its so important to be taught how to clean themselves, how to spread themselves out because any touch of urine to the labias labia majora and labia minora- the urine will be contaminated, so the urine has to flow freely and clearly, and of course the area has to be cleaned with anti-septic soap and dried with sterile gauzes, and we provide those to the pt. and we have instructions that they should follow properly, if they dont the specimen will be contaminated and then we will throw it out and look how much time and money we are going to lose.

Specimen transportation: -Then we need to transport the specimen to the lab and this should happen immediately in less than 12 hrs, more than 12 hrs the bacterial count that youll get might not reflect the actual pathology because bacteria will multiply in the urine.
because of that we dont accept urine specimens pt.s bringing them from home, because we are not sure when they have been collected, how they do that get collected so the specimen collection is so

important, when they get to the lab immediately we do urinalysis and then we culture after that.
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 If the pt. couldnt provide us with the midstream clean-catch specimen ex: the pt. is comatose, babies we can go into the urinary bladder directly by suprapubic aspiration: just above the public bone or the coccyx and so we are in the middle of the urinary bladder.

In prostatitis: we take many specimens we call them voided bladder.

VB1:The first specimen that we take is just the flow to wash the urethra we call it VB1 void bladder specimen number 1 -. VB2: is the midstream clean-catch. VB3: Then we do what we call Express prostatic massage, we massage the prostate, physician wears gloves and massages the prostate so if the prostate is infected pus will be coming out of the urethra and then we let the urine flow so it will wash the pus and the bacteria that will come out of the prostate and this is what we call VB3.

VB3 is the most important specimen that we rely upon to make a diagnosis of
prostatitis. And we culture that, and mainly bacteria that cause UTI are the ones that cause prostatitis. -Pyuria: we see pus cells in the urine, WBC casts (we talked about that) gram stain of uncentrifuged urine, one organism indicates UTI.

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 Chemical screening tests:sometimes initial screening before you send it to

culture you look for enzymes like:

- Leukocyte esterase we have like dipsticks, if you are sure that this enzyme is present then there is an infection and then you can proceed, if this enzyme is not present why to go through the pus culturing. -Nitrite which comes from nitrate the Enterobacteriaceae they reduce nitrate to nitrite, if nitrite is there that means we have Enterobacteriaceae infection then you proceed but those they are not that sensitive these are just new ideas on how to proceed with the diagnosis. So urine culture is the most important, Quantitative Bacteriology is the rule 105 Cfu/ml, but the count has to be correlated with the clinical presentation the count should be linked to symptoms-, sometimes we could adopt a low count in a pt. with symptoms, some pt.s could be on antibiotics.

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[The pic. In the previous page]--And this indicates the # of colony count and the

percentage of microscopic finding related to symptoms. -You can see here when we have a very high number 104 ,105 the correlation usually is so high infected- but sometimes in less numbers 103 usually is not but if the they are correlated with symptoms then maybe if the number is low we could take that in consideration. Treatment -Guided by the results of culture and susceptibility testing is the rule of thumb, i.e. if you send a specimen for culture and you dont wait for the results of the antibiogram then as if you have done nothing. And you can start with Empirical therapy, i.e. you should start with antibiotics that cover against mainly gram-ve bacteria waiting for the result of anti-biogram to come out then if that was susceptible you continue if not you switch. 1. Mainly the test antibiotic that we like to do is the TMP-SMX (TrimethoprimSulfamethoxazole), two antibiotics TMP + SMX we call it septra or bactrim it has an excellent susceptibility to gram-ve bacteria but cant replace antibiogram. 2. Flouroquinotones: these antibiotics have the ability to be excreted in the urine freely, not changed, it will be inappropriate to use an antibiotic that is not excreted changed like chloramphenicol we dont use these for the treatment of UIT, Flouroquinolone are very effective. 3. Ciprofloxacin, floxacins as well 4. Nitrofurantion, excreted in the urine unchanged 5. Many of the B-lactam antibiotics also the new ones can be used. But by literature and on statistics TMP-SMX is the drug of choice.

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-Treatment should be followed by culture and if the pt. is on antibiotics the pt. should continue the course, 10 days to 2 weeks, even if the pt. feels better, otherwise bacteria could develop resistance.

-Proper Hydration is the rule of thumb, the more you drink fluids the higher the chance you will recover fast, around 10-15 glasses of water.

Chemoprophylaxis: we can use it in honeymoon cystitis and so on, when its highly expected, in their first sexual experience they could develop that, so they could take a course of TMP-SMX, or when they do instrumentation and so on. -In many pt.s if the cause of UTI is not discovered properly then we have to do the intravenous pyelography (IVP) and now we have Ultrasound and CT scanning that can detect any congenital anomalies that could be present in the urinary tract. Btw you can find this in Sherris.

THE END ASEEL AL-HADER & NOMI AL-MOMANI

Thank you Raneem for your help =d 3llabnaki sette ;) --- This lecture is dedicated to the soul of the sweetest angelic Chris <3 Special thanks goes to ichigo-chan, Amnah & rana :))

Good Luck jme3an :)

Zulaikha Hairuddin

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