Dr. Sandeep Kumar Garg M.D (Internal Medicine) D.M (Nephrology)

Consultant NephrologistKidney Transplant Physician

MEERUT 9837285283www.sandepgargkidney.com

EPIDEMIOLGY UTI are the most common bacterial infection

Additionally , UTI is the most common cause ofnosocomial infection

Women make a significant proportion of UTI suffer”swith annual incidence of 12.1%

Peak incidence of UTI in women occurs between theages of 20-40 yrs

20-30% of women who have a UTI will have recurrentUTI(RUTI)

Epidemiology RUTI results in significant discomfort & have a high

impact on ambulatory health care cost as a result ofOPD visits, diagnostic tests & prescriptions.

RUTI is more common in post menopasal females dueto residual urine after voiding, which often associatedwith bladder or uterine prolaspe

In addition, the lack of estrogen causes markedchanges in vaginal microflora, including a loss oflactobacilli & increased colonization of E.Coli.

DEFINATION UTI is diagnosed in women by presence of at least

100,000 colony forming units (cfu)/ml in pure cultureof voided clean catch urine.

RUTI are caused by either re-emergence of bacteriafrom a site within the urinary tract (bacterialpersistence) or new infections from bacteria outsidethe urinary tract (reinfection).

RUTI is defined as three episodes of culture confirmedUTI in the last 12 mths or 2 episodes in last 6 mths.

RISK FACTORSWomen

Infections tend to recur.

Short urethra

Frequent sexual intercourse

Spermicidal cream

Diaphragm

.

RISK FACTORS

Menopausal females have decrease inestrogen, which leads to thinning of liningof the urinary tract, which increasessusceptibility to bacterial infections.

Pregnancy does not increase the risk ofgetting UTI but it can increase the risk ofdeveloping a serious infection that couldpotentially harm the mother & fetus

PATHOGENESIS The interaction between bacterial virulence & host

defense factors can ultimately results in UTI

More virulent bacteria are necessary to infecthealthy hosts with normal urinary tract, whereasless virulent bacteria may easily infectcompromised hosts

The cause of UTIs in women is usuallycolonization of the vagina & urethera with bacteriafrom the intestinal tract

BACTERIAL VIRULENCE

The initial step in pathogenesis of UTI is bacterialadherence to urothelium by pilli.

Pilli are filamentous adhesvie organelles inUropathogenic strains of E.coli (UPEC)

Bacterial colonization causes a host inflammatoryresponse, which includes neutrophil influx,followed by apoptosis & exfoliation of thebladder”s epithelial cells in an effort to rid thebladder of bacteria.

PATHOGENS IN UNCOMPLICATED UTI

E.Coli – 70 – 95 %

Staph Saprophyticus - 5- 20 %

Klebsiella

Entrococcus Faecalis

Proteus Mirabilis

HOST RISK FACTORS IN PATHOGENESISGenetic, anatomic, functional, & behavioralfactors that affect the host susceptibility touropathogens & its ability to overcome them.

Anatomical/FunctionalCongenital Abnormalties

Urinary Obstruction

Urinary Incontinence

Calculi

Residual Urine

Cathers or Foreign Bodies

Atrophic Vaginitis

Genetic

Blood group Antigen

Nonsecretor status

Density of adhesinreceptors

Behavioral

Sexual activity

Diaphragm use

Spermicide Use

Antimicrobial use

Risk Factors differ in Pre & Post Menopausal In sexually active pre-menopausal risk factors are:

Frequency of sexual intercourse

Spermicide Use

Age of First UTI (< 15 yrs of age indicates > risk of RUTI)

H/O UTI in the Mother (genetic factor or long term environmental exposures)

In Post menopausal risk factors are:

Vesical Prolaspe

Incontinence

Post Voiding residual Urine

Management of RUTI

Initial Evaluation of Females with RUTI Most women with RUTI do not have anatomic

abnormalities & do not need a X Ray

Assesment should include

History & physical Exam that include a pelvicexam

Pelvic USG for residual urine

Urine C/S for documenting that UTI is the cause ofsymptoms (typically , frequency, dysuria, &Haematuria)

Specialized Evaluation for RUTI

Congenital Abnormalities -

Either CT scan or IVP should be done

Prior Pelvic Surgery –

USG for checking HDN HU because of uretermay be caught in scarring due to stitch or clip during prior surgery

Cystoscopy to check the bladder for stitches which can form a nidus for stone or infection

Specialized Evaluation for RUTIUTI with Klebsiella, Pseudomonas or

Proteus bacteria – USG KUB is done becausethese bacteria have urease splitting enzymethat can alkalinize urine & may causeformation of struvite stones

Kidney Stones – check NCCT for stones,evidence of urinary obstruction.

Pyelonephritis – diagnosed by positive urineC/S , back pain and High fever

DIFFERENTIAL DIAGNOSIS OF RUTI Not all women with frequency, dysuria &

haematuria have UTI

In the case of RUTI, especially with negativecultures; a urogical & gynaecological evaluationshould be performed in order to exclude

Bladder cancer

Obstructive problems

Detrusor failure

Vaginal infections

Genital infection

Interstitial cystitis

Neurogical disease

Complications of RUTI

Acute Papillary necrosis

Overwhelming sepsis syndrome with shockdue to

Loss of vasomotor tone

Capillary Leak

Impaired myocardial performance

Perinephric abscess

TREATMENT of RUTI Primary Tt for RUTI should be guided by C/S

Commonly used antimicrobials that act on gramnegative uropathic organism include

Trimethoprim (TMP) & Co-trimoxazole (TMP-SMX)

Fluroquinolones (ciprofloxacin, levofloxacin, norfloxacin,ofloxacin, moxifloxacin)

Nitrofurantin

Beta–Lactams penicillins (amoxycillin, ampicillin-likecompounds, cefadroxil, cefuroxime, cefpodoxime)

Duration of Tt of 7-10 days increases rate of eradication& minimize resistance to drugs

DOSES RECOMMENDED

PREVENTION OF RUTIApproaches proposed for the prevention:

Non Pharmacological therapies,

Local estrogens for post menopausalfemales

Antimicrobial prophylaxis therapy: givenregularly or postcoital prophylaxis insexually active women

Immunoactive Prophylaxis

NON PHARMACOLOGICAL THERAPIESNon Pharmacological therapies have

doubtful role & include:

Adequate fluid intake

Voiding after sexual intercourse

Ingestion of cranberry juice

Eating yogurt ( lactobacilli Cultures)

Vaginal application of lactobacilli

Avoiding constipation

PROPHYLACTIC ANTIMICROBIAL

Continuous prophylactic antimicrobialtherapy

Post coital antimicrobial therapy

Self start antimicrobial therapy

CONTINUOUS PROPHYLACTIC ANTIMICROBIAL THERAPY

One effective approach for Mgmt is the prevention ofinfection by use of long term, prophylacticantimicrobials taken on a regular basis at bedtime

It is not known

Which antibiotic schedule is best

Optimal duration of prophylaxis

Incidence of adverse events

Recurrence of infections after stopping prophylaxis

Treatment compliance

CHOICE OF ANTIBIOTIC

TMP, Co-trimoxazole or nitrofurantin canstill be considered as the standard regimen.

In cases of Breakthrough infection due toresistant pathogens, low doses offlouroquinolones may be used

During pregnancy an oral first – generationcephalosporin is recommended

POST COITAL ANTIMICROBIAL THERAPY

It is an alternative prophylactic approach forwomen in whom episodes of infection areassociated with sexual intercourse

Same drugs can be used in the same doses asrecommended for continous prophylaxis

SELF START ANTIMICROBIAL THERAPYSuitable for mgmt in well informed women

in whom the rate of recurrent episodes isnot too common

This is not prophylaxis but early treatment

It has emerged in an effort to decreaseoverall antibiotic usage

It relies on pt’s intelligence andrecognization of UTI

Pt takes same antibiotics for 2-3 days

EFFICACY & SIDE EFFECT OF PROPHYLACTIC THERAPYNumber of pts with RUTI decreased by

eightfold after prophylaxis

UTI episode /pt year is reduced by 95%during prophylaxis

However, prophylaxis does not appear tomodify the natural history of RUTI or exerta longterm effect on the baseline infectionrate

EFFICACY & SIDE EFFECT OF PROPHYLACTIC THERAPYAfter stopping prophylaxis even after

extended periods, approximately 60 % ofwomen will become re–infected within 3-4mths

Side effects of prophylactic antimicrobialsinclude vaginal & oral candidiasis and GIsymptoms

RUTI IN PREGNANCYWomen with bacteria in urine during

pregnancy should be put on prophylaxis tilldelivery (penicillin or first generationcephalosporin)

Other options for pts whom are allergic isNFT or TMP-SMX

Women with bacteria with no symptoms andwhom are not pregnant do not need to betreated with antibiotics

CRANBERRY Cranberry (Botanical name - Vaccinium macrocarpon)

is a small evergreen shrub grown in bogs in dampforests and open ponds. It requires wet, boggy, acidicsoil

CRANBERRYCranberry is a North American native

Cranberry was a popular Tt of UTI prior tothe introduction of antibiotics, & continuesto be used widely for this purpose.

Cranberries (Proanthocyanidin) can inhibitthe attachment of bacteria to the epitheliallining of the urinary tract.

In vitro studies have observed potentinhibition of bacterial adherence of E.coli &other gram-negative uro-pathogens.

CONCLUSIONS FROM STUDIES

Cranberry has direct antibacterial activityCranberry may offer an alternative

methodology to antibiotic prophylaxis.Effect on type P-fimbriated E. coli was

observed to be specific to cranberry400 mg / day of shows reduction in RUTI In one uncontrolled study, more than 50%

of pts had a positive clinical response in UTI

D-MANNOSED-Mannose is a sugar monomer of the

alsohexose series of carbohydrates. Mannoseis a C-2 epimer of glucose.

D-mannose prevents binding of type 1-piliated E. coli to the human bladder cell line& reduces both adhesion & invasion of theE.coli.

It significantly reduce bacteriuria within 1day

Pts who were treated daily with D-Mannose,94% reported symptom improvement.

THE RIGHT COMBINATION‘ALTERNATIVE MEDICINE REVIEW’

suggests the use for Cranberry & D-Mannose as a natural option for the

mgmt of UTI. At the same time, Potassium salts are suggested to

alkalize the urine and reduce dysuria.

URIKIND-KM SACHETCranberry Extract...200mgD-Mannose...300mgPotassium Magnesium Citrate...978mgPer 5gm Sachet

Recommended doses:1 Sachet BID in 200ml water.

INPATIENT CARE FOR RUTI Necessity of admission depends upon Age, Host

factors, Risk of complicated infection, Likelihood ofmorbidity with failed OPD treatment

Pts with

Structural abnormality ( eg, calculi, Urinary tractabnormality , indewelling catheter , obstruction)

Metabolic disease ( eg, DM, CKD)

Impaired Host defense ( eg, HIV, Currentchemotherapy, underlying active

INPATIENT CARE FOR RUTIPts with uncomplicated Pyelonephritis

should be admitted

Pts unable to maintain oral hydration, shock, fever unresponding to antipyretic therapy

Pts with deblitating pain or dehydration that cannot be corrected in OPD

Pts with inadequate home care or resources to comply with medical regimen

TAKE HOME MESSAGE RUTI are a major issue for many women because

they are common, costly, & cause considerablemorbidity

Pts with RUTI should be properly investigatedby Lab & radiological techniques to excludecomplicated causes or gynecological problems.

Prophylactic therapy proved efficacy withdecrease rate of recurrence, minimal sideeffect & drug resistance but without alterationin natural history of disease

Thanks