ANTIBIOTICs FOR URINARY

TRACT

dr. Ave Olivia Rahman, MSc.

Bagian Farmakologi FKIK UNJA
 Urinary Tract Infection (UTI)
• Causative : Bacterias  Escherichia coli (80%),
Staphylococcus saprophyticus (5- 15%),
Enterococci, Klebsiella species and Proteus
mirabilis
• Location :
– Upper Urinary Tract : pyelonephritis
– Lower Urinary Tract : cystitis, urethritis,
prostatitis, and epididymitis
• Complicated, Uncomplicated.
• Recurrent : Persistence, Reinfection.
 Empirical Antibiotics for
uncomplicated UTIs
1. Trimethoprim–sulfamethoxazole
2. Fluoroquinolones: Ciprofloxacin, Levofloxacin
3. Beta-lactams : Groups of Cephalosporins,
amoxicillin–clavulanate.
4. Macrolide: clarithromycin, azithromycin,
erytromycin used in STD-caused UTIs.
5. Antiseptics : nitrofurantoin, methanamine
 Factors When Selecting An Antibiotic
For A Urinary Tract Infection

• Patient's allergy history

• The cost and tolerability of the treatment,
• Previous antibiotic therapy,
• The prevalence of resistance in the
community.
 Co-trimoxazole
• Bacteriostatic.
• Inhibiting folic acid synthesis  decreases the
number of bacterial nucleotides and inhibits
bacterial growth.
• Pregnancy: Trimethoprim is unlikely to cause
problems in women with normal folate status
(NO TERATOGENIC), but may cause problems
in women who have a folate deficiency or low
folate intake
 Continue...Dosing for UTIs
• Acute Uncomplicated Cystitis (as first-line
therapy): 2x 160 mg and 800 mg for 3 day.
• Acute Uncomplicated Pyelonephritis :TMP-
SMX 2x 160 mg and 800 mg for 14 days.
 amoxillin/amoxillin-clavulanate
• Groups of pennicillin
• bactericidal, wide a spectrum.
• Interact with bacteria’s enzym penicillin-
binding proteins (PBPs)  inhibits cell -wall
synthesis.
• Pregnancy : category B
 Continue...Dosing for UTIs
• Acute Uncomplicated Cystitis (as Second-line
therapy) : amoxicillin–clavulanate for 3 to 7
days.
• acute uncomplicated pyelonephritis:
amoxicillin–clavulanate 14 days
 Cephalosporins
1. First -generation : cefadroxil, cefazolin sodium,
and cephalexin monohydrate.
2. Second -generation : cefaclor, cefprozil,
cefoxitin, cefuroxime axetil, and cefuroxime
sodium.
3. Third -generation : cefdinir, cefixime, cefotaxime
sodium,cefpodoxime proxetil, ceftazidime,
ceftibuten, and ceftriaxone sodium.
4. Fourth -generation : cefepime hydrochloride.
 Continue...Cephalosporins
• Similiar with penicillins in structure and
mechanism of action.
• First -generation act primarily against gram –
positive organisms.
• Second -generation act against gram -negative
bacteria.
• Third -generation which act primarily against
gram –negative organisms.
• Fourth -generation act against many gram -
positive and gram - negative bacteria.
 Continue...Dosing for UTIs
• Acute Uncomplicated Cystitis (as Second-line
therapy): cefdinir, cefaclor, and cefpodoxime–
proxetil for 3-7 days.
 Fluoroquinolones
• Ciprofloxacin, Levofloxacin, Moxifloxacin,
Norfloxacin, Ofloxacin.
• Inhibiting DNA gyrase in bacteria Interrupt
deoxyribonucleic acid (DNA) synthesis during
bacterial replication.
• Pregnancy : Category B
 Continue...Dosing for UTIs
• Acute Uncomplicated Cystitis (as Second-line
therapy) : Ciprofloxacin 2x250 mg for 3 days;
levofloxacin 1x 250-500 mg once for 3 days.
• Acute Uncomplicated Pyelonephritis:
Ciprofloxacin 2x 500 mg or 1x1 g (extended–
release) for 7 days; levofloxacin 1x 750 mg for
5 day.
 Broad Spectrum Antibiotics
• The use of broad spectrum antibiotics (such
as cephalosporins, penicillins) should be
avoided when a narrow spectrum antibiotic
would be more appropriate.
• There are concerns that broad spectrum
antibiotics increase the risk of Clostridium
difficile, methicillin-resistant Staphylococcus
aureus (MRSA) and resistant UTIs.
 Antiseptic
• METHANAMINE, NITROFURANTOIN
• The urinary tract antiseptics are concentrated
in the renal tubules inhibit growth of many
bacteria.
• Cannot be used to treat systemic infections 
effective concentrations are not achieved in
plasma with safe doses.
• As local therapy  only in kidney and bladder
 Methenamine
• Prodrug
• Generate formaldehyde that have
antibacterial action.
• Acidification of the urine promotes the
generate of formaldehyde  should strive to
keep the pH below 5.5
 Continue...Antimicrobial Activity
• Nearly all bacteria are sensitive to free
formaldehyde, at concentrations 20 μg/ml.
• Urea-splitting microorganisms (e.g., Proteus
spp.) tend to raise the pH of the urine 
inhibit the release of formaldehyde.
• Microorganisms do not develop resistance to
formaldehyde
 Continue...Pharmacology
• Absorbed orally. 10-30% decomposes in the
gastric juice (unless protected by an enteric
coating)
• Produce ammonia  contraindicated in
hepatic insufficiency.
• The acids commonly used are mandelic acid
and hippuric acid (UREX, HIPREX).
 Continue...Toxicology
• Gastrointestinal distress
• Painful and frequent micturition, albuminuria,
hematuria, and rashes.
• CONTRAINDICATION: in renal insufficiency 
can occur crystalluria
• Methenamine combines with sulfamethizole
 mutual antagonism.
 Continue...Therapeutic Uses and Status

• Not a primary drug for the treatment of acute

urinary tract infections, but it is of value for
chronic suppressive treatment.
• Most useful for E. coli, the common gram-
negative offenders and often S. aureus and S.
epidermidis .
• Enterobacter aerogenes and Proteus vulgaris
are usually resistant.
 Nitrofurantoin
• A synthetic nitrofuran
• Formed highly reactive intermediates  damage
DNA.
• Active against E. Coli and enterococci.
• Resistant for Proteus, Pseudomonas, Enterobacter
and Klebsiella.
• The antibacterial activity is higher in an acidic urine.
• Bacterial resistance to nitrofurantoin is frequent .
• Not recommended for treatment of pyelonephritis or
prostatitis.
 Continue...Pharmacology
• Absorbed rapidly and completely from the GI
tract.
• Drug is eliminated rapidly Antibacterial
concentrations are not achieved in plasma.
• Plasma half-life is 0.3 to 1 hour. 40% is
excreted unchanged into the urine.
• In impaired glomerular function  efficacy
of the drug and  systemic toxicity.
• Nitrofurantoin colors the urine brown.
 Continue...Toxicology
• Gastrointestinal upset, Hypersensitivity
reactions, leukopenia, hemolytic anemia
[associated with G6PD), hepatocellular
damage, Acute pneumonitis, Interstitial
pulmonary fibrosis, Megaloblastic anemia,
neurologic disturbance.
• CONTRAINDICATION : Pregnant women (>36
week), impaired renal function (creatinine
clearance < 40 ml/min), and < 1 month of
age.
 Dosing of Nitrofurantoin
• Adults dose : 4x 50 to 100 mg/day, with
meals and at bedtime.
• Child dose : 5 to 7 mg/kg in 4 divided doses
(max 400 mg).
• Prevent recurrences : A single 50-100mg dose
at bedtime .
• A course of therapy should not exceed 14
days, and repeated courses should be
separated by rest periods.
 Guideline..(example)
• Paracetamol can be used to relieve pain
associated with UTIs
• Treat non-pregnant women of any age with
symptoms or signs of acute LUTI with a three day
course of trimethoprim or nitrofurantoin (B)
• Treat bacterial UTI empirically with a quinolone in
men with symptoms suggestive of prostatitis (B)
• Treat non-pregnant women with symptoms or
signs of acute UUTI with a course of ciprofloxacin
(7 days) or co-amoxiclav (14 days). (D)
 Post Test
1. Antibiotik yang dapat digunakan untuk infeksi
saluran urinari antara lain ....
2. Antibiotik lini pertama untuk sistitis .....
3. Nitrofurantoin merupakan golongan..... dapat
digunakan untuk terapi sistitis/pielonefritis?
4. Mekanisme kerja methenamine ....
 Kasus 1
• Ny. T, 50 tahun, mengeluh BAK sering dan
sedikit nyeri, panas. Sebelumnya pernah
mengalami hal serupa, kira-kira 2 tahun
yang lalu. Nyeri tekan suprasimfisis
pubis(+), suhu 38C. Dokter mendiagnosis
sistitis ec bakteri. Sarana laboratorium
jauh, sehingga dokter memutuhkan
memberikan terapi antibiotik secara
empiris. Berikan resep untuk pasien tsb!
 Kasus 2
• Ny. S, 45 tahun mengeluh deman dan keluhan
ISK. didiagnosis pielonefritis akut. Berikan
resep untuk pasien tersebut.
• R/ paracetamol 500 mg tab no IX
– Stdd tab 1 prn
R/ co—trimoxazol 80;400 mg mg tab VI
S 0 12 h tab 1