URINARY TRACT

INFECTION (UTI)
Fifteen Aprila Fajrin
Faculty of Pharmacy
Jember University
Outlines…
1)  Definition  
2)  Epidemiology  
3)  Classification  
4)  Pathogenesis  
5)  Drug  therapy  
6)  Cases  
 à Is  a  common  disorder  
à Defined  as  the  presence  of  microorganism  in  the  
urinary  tract    
à Most  commonly  occuring  bacterial  infection  à  
antibiotics  treatment  
à Normal  urinary  tract  is  usually  resistant  to  infection  
à Female  urinary  tract  is  more  susceptible  to  infection  
à   almost  half  of  women  have  at  least  one  UTI  
à   the  risk  of  UTI  in  women  increase  after  
UTI? menopause    
 Epidemiology
Grade  school  and  before  puberty  à  
Varies  with  age  and  gender 1%  dan  increasing  to  1-­‐4%  after  
puberty  in  females.  In  males  is  very  
low  

New  born  and  infant  (up  to  6  mo)  à   Among  20-­‐50  yr  old  à  50  fold  more  
CONTENTS
boys  à  abnormalities  of  the  urinary   TITLE common  in  women.
tract  and  noncircumcision

In  elderly  >  65  yr  old  à  equal  

1-­‐6  yr  old  à  females between  women  and  men
 Anatomy of Urinary Tract

①  Upper  tract    
-  Kidney  
-  Ureter    
②  Lower  tract  
-  Bladder  
-  Urethra    
 Classification…
Anatomy  
1.  Upper  (pyelonephritis)  
2.  Lower  (cystitis)  

Complication  
1.  Complicated  
-  Result  of  a  lession  of  the  urinary  tract  ex:  congenital  abnormality,  a  
stone,  indwelling  catheter,  prostatic  obstruction,  neurologic  disorder  
-  In  both  gender  
2.  Uncomplicated  
-  Structural/functional  abnormalities  of  urinary  tract  
-  Women  à  15-­‐45  yo  
-  Men  à  very  rare  
Location  
1.  Hospital  
2.  Community  
 Etiology

-  Most  UTI  are  caused  by  single  organism  

-  The  bacteria  causing  UTI  à  bowel  flora  of  the  host  
-  Most  common  cause  of  uncomplicated    UTI  à  
Escherichia  coli  (80-­‐90%  in  community)  
-  Most  common  in  complicated  UTI  à  E.  coli  (around  
50%  of  infection)  and  Enterococci  is  the  second  most  
frequently  in  hospitalized  patients  
 Men and women with • Extrarenal obstruction associated with congenital anomalies of the ureter or urethra, calculi,

Etiology
structural abnormalities extrinsic ureteral compression, or benign prostate hypertrophy
• Intrarenal obstruction associated with nephrocalcinosis, uric acid nephropathy, polycystic
kidney disease, hypokalemic or analgesic nephropathy, renal lesions from sickle cell disease

UTI = urinary tract infection.

Information from: Grabe M, Bartoletti R, Bjerklund Johansen TE, et al, for the European Association of Urology. Guidelines on
Urological Infections. 2015; and Sobel JD, Kaye D. Urinary tract infections. In: Mandell GL, Bennett JE, eds. Principles and Practice
of Infectious Diseases, 8th ed. Philadelphia: Elsevier Saunders, 2014:886-913.

Table 1-2. Uropathogens by Type of UTIs

Type Common Uropathogens

Uncomplicated UTI E. coli

S. saprophyticus
Enterococcus spp.
K. pneumoniae
P. mirabilis

Complicated UTI Similar to uncomplicated UTI

Antibiotic-resistant E. coli
P. aeruginosa
Acinetobacter baumannii
Enterococcus spp.
Staphylococcus spp.

CA-UTI P. mirabilis
Morganella morganii
Providencia stuartii
C. urealyticum
Candida spp.

Recurrent UTI P. mirabilis

K. pneumoniae
Enterobacter spp.
Antibiotic-resistant E. coli
Enterococcus spp.
Staphylococcus spp.

CA-UTI = catheter-associated urinary tract infection; UTI = urinary tract infection.

Information from: Sobel JD, Kaye D. Urinary tract infections. In: Mandell GL, Bennett JE, eds. Principles and
Practice of Infectious Diseases, 8th ed. Philadelphia: Elsevier Saunders, 2014:886-913.

PSAP 2018 BOOK 1 t Infectious Diseases 9 Urinary Tract Infections

Risk Factor of UTI
 ①  Route  of  infection  
②  Host  defense  mechanism  
③  Bacterial  virulence  factor  

Pathophysiology
① Route of infection
②  Host defense mechanism
③ Bacterial virulence factor
Clinical
Presentation Lower  UTI  à  dysuria,  nocturia,  
suprapubic  heaviness

Gross  hematuria

Upper  UTI  à  flank  pain,  fever,  

nausea,  vomiting,  malaise

LABORATORIUM  TEST  à  

-  Bacteriuria  
-  Pyuria  (WBC  count  >  10/mm3)  
-  Nitrite-­‐positive  urine  
-  Leukocyte  esterase-­‐positive  urine  
-  Antibody  coated  bacteria  (upper  UTI)
Clinical
Presentation
Pyuria  

Hematuria  

Bacteriuria  
 Diagnostic Criteria for Significant
Bacteriuria

Description   Condition  
≥  102  CFU  coliforms/mL  (≥  105  CFU/L)  atau  ≥  105  CFU   Symptomatic  female  
noncoliforms/mL  (≥  108  CFU/L)  
≥  104  CFU  bacteria/mL  (≥  107  CFU/L)   Symptomatic  male  
≥  105  CFU  bacteria/mL  (≥  108  CFU/L)   Asymptomatic  individuals  on  two  consecutive  
specimens  
 
Any  growth  of  bacteria  on  suprapubic  catheterization  
in  a  symptomatic  patient  
≥  102-­‐5  CFU  bacteria/mL  (≥  105-­‐8  CFU/L)   Catheterized  patient  

*CFU:  colony  forming  unit  

 Goal’s Theraphy
①  to  eradicate  the  invading  organism(s)  
②  to  prevent  or  to  treat  systemic  consequences  of  infection  
③  to  prevent  the  recurrence  of  infection  
④  to  decrease  the  potential  for  collateral  damage  with  too  broad  of  antimicrobial  therapy.  

①  Acute  uncomplicated  cystitis    

②  Symptomatic  abacteriuria,    
Therapy? ③  Asymptomatic  bacteriuria,    
④  Complicated  UTIs,    
⑤  Recurrent  infections  
 Acute uncomplicated cystitis
-  The  most  common  form  of  UTI  
-  Usually  in  women  of  childbearing  age  dan  often  are  related  to  sexual  activity  
-  Predominantly  caused  by  E.  coli  
-  Causative  organisms  are  known  à  initiation  of  empirical  therapy  without  urine  culture  
-  Acute  cystitis  is  a  superficial  mucosal  infection  à  eradicated  with  shorter  courses  of  therapy  (3  days)  
-  Advantages  of  short  course  therapy:  
-  Increased  adherence  
-  Fewer  side  effects  
-  Decreased  cost  
-  Less  potential  for  causing  resistance  
-  Antibiotics  of  choice:  
-  Trimethoprim-­‐sulfamethoxazole  
-  Fluoroquinolone  (ciprofloxacin,  levofloxacin)  à  excellent  efficacy  
-  For  5  days  course  à  nitrofurantoin  or  fosfomycin  or  in  area  where  is  more  than  20%  resistance  of  E  coli  
-  Amoxicillin  or  Ampicillin  à  avoided  because  of  E  coli  resistance,  if  it  have  to  be  beta  lactam  à  choice:  amoxi-­‐clav,  
cefdinir,  cefachlor  
 Acute
uncomplicated
cystitis
 Bacterial Cystitis: Antibiotic Options

Fluoroquinolones   TMP/SMX   Nitrofurantoin  

§ First  choice  in  some    guidelines   § Efficacious  against   § Efficacious  against  

uropathogens   E.  coli  
§ Broad  spectrum   § No  effect  on  vaginal  or  fecal   § No  adverse  effect  on  fecal  flora  
flora  

§ Excellent  side  effect  profile   § Few  side  effects  if  duration   § Narrow  spectrum  
short    
§ Little  resistance   § Increasing  resistance  (19%)     § Significant  adverse  event    
  profile  
 Symptomatic Abacteriuria
-  =  acute  urethral  syndrome  
-  Female  à  dysuria  and  pyuria,  but  urine  culture  <105  bacteria/mL  à  significantly  bacteriuria  without  
symptoms.  
-  Infected  with  small  number  of  coliform  bacteria:  E  coli,  Staphylococcus  spp,  Chlamydia  
trachomatis  
-  If  antimicrobial  therapy  is  innefective  à  a  culture  should  be  obtained.  
-  If  patient  reports  recent  sexual  activity  à  therapy  for  C  trachomatis  should  be  considered  
-  Treatment  à  azithromicin  1  g  or  doxycyclin  100  mg  twice  daily  for  7  days  
 Asymptomatic Bacteriuria (ASB)
-  ASB  is  the  finding  of  two  consecutive  urine  cultures  >  105  organism/mL  of  the  same  organism  in  
the  absence  of  urinary  symptoms  
-  Mostly  are  elderly,  female,  pregnant  women  
-  Relapse  and  reinfection  à  very  common  and  chronic  ASB  is  difficult  to  eradicate  
-  Management  of  ASB  depend  on:  age  and  condition  (pregnant/not)  
-  Usually  associated  with  Chlamidia  infection  
Complicated UTI
 Acute Pyelonephritis
-  Presentation:  high-­‐grade  fever  and  severe  flank  pain  à  hospitalized  and    iv  antimicrobial  
-  Mild  cases  à  orally  antibiotics  
-  Urine  culture  is  needed  
-  Mild-­‐moderate  à  7-­‐14  days  treatment,  depends  on  the  agent  
-  1st  line  choice:  fluoroquinolones  (ciprofloxacin  or  levofloxacin)  orally  7-­‐10  days  
-  Other  options  à  trimethoprim-­‐sulfamethoxazole  for  14  days  
-  If  amoxi-­‐clav  are  used,  give  an  initial  parenteral  antibiotic  first  such  as  ceftriaxone  then  continued  to  oral  
administration  for  10-­‐14  days  
-  If  positive  gram  bacteria  was  found  à  ampicillin  
-  Severe  à  broad  spectrum  bacteremia  or  sepsis  
-  Fluoroquinolone  or  aminoglycoside  with  or  without  ampicillin  
-  Extended-­‐spectrum  cephalosporins  with  or  without  an  aminoglycoside  
-  Other:  aztreonam,  beta-­‐lactamase  inhibitor  combination,  carbapenem,  iv  trimethoprim-­‐sulfamethoxazole  
-  Hospitalized  patient  >  6  month  à  +  catheter  à  P  aeruginosa  dan  enterococci  
-  Therapy  ceftazidime,  ticarcilin-­‐clavulanate,  piperacilin,  aztreonam,  meropenem  or  imipenem  in  combination  
with  aminoglicosides  
 Urinary Tract
Infection in Males
-  Management  of  UTI  in  males  more  difficult  than  in  
female  
-  Incidence  in  males  <  60  yo  less  than  females  
-  Most  common  cases:  catheterization  and  stone  in  renal  
or  urinary  tract  
-  Uncomplicated  infection  à  rare  à  young  males  as  the  
result  of  homosexual  activity,  noncircumcision  and  
having  sex  with  infectious  partner  
-  As  aging  à  most  common  cause  is  because  bladder  
outlet  obstruction  (in  prostatic  hyperthrophy)  
-  Urine  culture  should  be  obtained  before  treatment  à  
unpredictable  causes  
-  Gram  negative  à  1st  trimethoprim-­‐sulfamethoxazole  or  
quinolone  for  10-­‐14  days    
Recurrent Infections
-  Most  commonly  are  female  à  20%  of  females  with  cystitis  
-  Reinfection  divided  into:  
-  <  3  episodes/year  
-  >  3  episodes/year  
-  Before  prophylaxis,  patients  are  treated  conventionally  with  
-  Trimethoprim-­‐sulfametoxazole    (one-­‐half  of  asingle-­‐strength  
tab)  
-  Trimethoprim  (100  mg)  
-  Fluoroquinolone  (levofloxacin  500  mg  daily)  
-  Nitrofurantoin  (50  or  100  mg  daily)  
-  Therapy  à  6  month,  followed  urine  cultures  
-  Women  with  symptomatic  reinfection  in  association  with  sexual  
activity  à  1st  trimethoprim-­‐sulfamethoxazole  
-  Postmenopausal  women  à  lack  estrogen  à  changes  in  the  
bacterial  flora  of  the  vagina  à  increasing  E  coli  
-  Estrogen  cream  
 Special Condition-UTI in Pregnancy
-  Severe  vasodilatation  of  the  renal  pelvis  and  ureters,  decreased  ureteral  peristalsis  and  reduced  bladder  tone  
-  Cause  urinary  stasis  and  reduced  defences  against  reflux  of  bacteria  to  the  kidney  
-  Increased  urine  content  of  amino  acids,  vitamins,  nutrient  à  increasing  bacterial  growth  
-  Resulting  symptomatic  infections,  trimester  
-  ASB  à  4-­‐7%  pregnant  patients  à  20-­‐40%  will  develop  to  acute  symptomatic  pyelonephritis  
-  Untreated  à  prematurity,  low  birth  weight  
-  E  coli  
-  Therapy  à  7  days,  low  adverse  effect  dan  safe  for  mother  dan  the  baby  
-  Choice:  
-  Amoxicillin  
-  Amoxi-­‐clav  
-  Cephalexin  
-  Nitrofurantoin  à  with  caution  
-  Avoid  tetracyclines  (à  teratogenic  effect)  dan  sulfonamides  (in  3rd  trimester  à  kernicterus  and  
hyperbilirubinemia)  
-  Avoid  fluoroquinolones  à  potential  effect  on  inhibition  of  cartilage  and  bone  development  in  newborn
 Special Condition-Catheterized Patient

-  Factor  
-  Method  and  duration  of  catheterization  
-  The  catheter  system  (open/closed)  
-  The  technique  of  healthcare  personnel  
-  5%  patient/day  
-  Closed  system  à  prevents  bacteriuria  for  10  days  
-  After  30  days  catheterization  à  incidence  of  bacteriuria  increase  into  78-­‐95%  
-  Prophylactic  systemic  antibiotics  in  short-­‐term  catheterization  patient  à  reduces  infection  for  the  first  
4-­‐7  days    
-  Prophylactic  systemic  antibiotics  in  long-­‐term  catheterization  à  postpone  the  development  of  
bacteriuria  and  lead  to  the  emergence  of  resistant  microorganism  
 TABLE 116-3  Overview of Outpatient Antimicrobial Therapy for Lower Tract Infections in Adults
Indications Antibiotic Dose Interval Duration
Lower tract infections
Uncomplicated Trimethoprim–sulfamethoxazole 1 DS tablet Twice a day 3 days
Nitrofurantoin monohydrate 100 mg Twice a day 5 days
Fosfomycin trometamol 3g Single dose 1 day
Ciprofloxacin 250 mg Twice a day 3 days
Levofloxacin 250 mg Once a day 3 days
Amoxicillin–clavulanate 500 mg Every 8 hours 5-7 days

Pivmecillinam 400 mg Twice a day 3 days

Complicated Trimethoprim–sulfamethoxazole 1 DS tablet Twice a day 7-10 days
Ciprofloxacin 250-500 mg Twice a day 7-10 days
Levofloxacin 250 mg Once a day 10 days
750 mg Once a day 5 days
Amoxicillin–clavulanate 500 mg Every 8 hours 7-10 days
Recurrent infections Nitrofurantoin 50 mg Once a day 6 months
Trimethoprim–sulfamethoxazole 1/2 SS tablet Once a day 6 months
Acute pyelonephritis Trimethoprim–sulfamethoxazole 1 DS tablet Twice a day 14 days
Ciprofloxacin 500 mg Twice a day 14 days
1,000 mg ER Once a day 7 days

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TABLE 94-5Evidence-Based Empirical Treatment of Urinary Tract Infections and
Prostatitis
Thank You