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Drugs Used in UTI & STDs

UTI Principles of Antibacterial Therapy

Uncomplicated
Healthy person esp women
No underlying risk factor
Complicated
↑ Risk for infection
• Men, Children, Pregnancy
• Structural, Neurological
abnormalities of urinary tract
• Metabolic/ hormonal
abnormalities
• Impaired host response
↑ Potential for serious outcome
↑ Risk of Treatment Failure

Etiology of UTI
Community Acquired Hospital Acquired
Gram –ve Aerobes from GIT E-coli
• E-coli Pseudomonas aeruginosa
• Coagulase-negative staph Proteus, Enterobacter, Serratia,
Enterobacteriaceae Acinetobacter
• Proteus mirabilis Staphylococcus aureus
• Klebsiella (hematogenous spread )
Enterococcus faecalis

Treatment Goals
Eradicate Infection effectively
Prevent associated Complications
↓ Adverse effects of drug therapy
↓ Cost of treatment
Considerations
Pathogens likely to cause infection
Resistance rate (various antimicrobials within specific geographic area)
(use discouraged if resistance rate > 15-20%)
Duration of treatment
Efficacy, Toxicity of various agents
Cost of each agents

Choice of Drugs
Excreted via Kidneys (unchanged)
↑ Half life
Frequency of treatment
Improve compliance
STD
↓ Side effects (be8 er compliance )
Bacterial Viral Mycoplasma Protozoal Fungal
Suited local bacterial sensitivity patterns
Easy administration – Oral, IV Gonorrhoea AIDS Non- Trichomoniasis Vaginal
gonococcal candidiasis
urethritis
Duration of Treatment
Syphilis Herpes
Considerations
genitalis
Type of Antibiotics used
UTI is complicated/ non -complicated Chancroid Viral
hepatitis
Uncomplicated cystitis (women) – 1 week
Non-
Longer (7-14 days)
gonococcal
Pregnancy
urethritis
Elderly
Infant
Syphilis
Pyelonephritis
4-6 weeks
Relapse with same organism
Diabetic, Polycystic Kidneys, Renal transplant
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Drugs used in UTI

Sulfamethoxazole (SMX) Trimethoprim (TMP) Quinolones Nitrofurantoin Ampicillin, Amoxycillin Cephalosporins Aminoglycosides
Sulfonamide group Active against Gram –v e bacteria and some gram +ve Well absorbed Extended spectrum Penicillin Beta Lactam Antibiotics No oral preparation
Bacteriostatic Bacteriostatic Block bacterial DNA Synthesis by Inhibiting Bacterial Rapidly excreted into Urine (aminopenicillin) MOA & Toxicity (poor absorption)
Gram +v e, Gram –ve Concentrates in Topoisomerase II Topoisomerase IV • No systemic Antibacterial Bactericidal for growing cells Similar to Penicillin Parenteral
Chlamydia trachomatis Vaginal fluids (DNA Gyrase) action achieved Beta Lactam Antibiotics ↑ Stable than Penicillins to Excreted unchanged via Kidney
Protozoa Prostate Prevent relaxation of +vely Interfere with separation of • Activity enhanced in ↓pH Well absorbed bacterial lactamases Used in in-patient treatment
Enteric bacteria Urine supercoiled DNA required for replicated chromosomal DNA (do not alkalinize urine) (amoxycilin better absorbed) • Broader spectrum of Affect Renal Function
(E.coli, Klebsiella, Salmonella, st
1 line treatment & prophylaxis normal transcription & into respective daughter cells • Urinary antiseptics Impaired by food activity Gentamicin
Shingella, Enterobacter) for UTI replication during division (antibacterial activity in (take 1-2h before meal) • Not useful against Amikacin
urine with little/no enterococci, listeria MOA
systemic effects) monocytogenes Block initiation complex
Excreted via urine
Non Fluorinated Quinolones Fluoroquinolones Can be given IV Miscoded peptide chain
Adverse Effects Adverse Effects Nalidixic acid Synthetic Fluorinated Excretion into Urine via Gram +v e, Gram –ve cocci Used in Block Translocation
st
Urticaria, Stev en-Johnson Megaloblastic anaemia 1 Quinolone analog of Nalidixic acid GFR & Tubular secretion (able to penetrate gram –v e Resistant UTI cases
syndrome Leukopenias (less) Excreted too rapidly into urine Improved antibacterial activity (in Renal Failure, outer membrane unlike Complicated UTI
Nausea, Vomiting, Diarrhea (unable to achieve Systemic (broad spectrum) ↓ Efficacy & Toxicity) penicillin) Cephalexin, Cefaclor, Cefixime
Stomatitis, Arthritis Antibacterial Concentration) Able to achieve Systemic Bacteriostatic, Bactericidal for Anaerobes Treatment
Haemolysis (G6PD Deficiency) Useful only for Lower UTI Antibacterial concentrations many Gram +ve, Gram -ve Enterococci Prophylaxis
• Kernicterus E.coli, Enterobacter, Klebsiella, Listeria ↑ Cost
↓ Absorption with Antacids Not effective ag ainst
(↑ risk newborns – taken Proteus (avoid) Pseudomonas aeruginosa & E.coli
end of pregnancy) Proteus infection H. Influenza (↑ dose)
Adverse Effects Adverse Effects MOA Not useful against
False +ve Glycosuria (Generally well tolerated) • Unknown Klebsiella
GIT Upset (Minimal adverse effec ts) • Cause bacterial DNA Enterobacter
Nausea damage (suggest) Pseudomonas aeruginosa
Vomiting Adverse Effects Indole +ve Proteus
Indication Anorexia MOA
• Reserv ed for complicated Nausea Inhibition of cell wall synthesis
cases Haemolysis (G6PD Deficiency) Inhibit Transpeptidation
Steven-Johnson Syndrome • Not responding to
cotrimoxazole
• Basis of Bacteriological
sensitivity
• Due to ↑ cost with UTI in Pregnancy
similar efficacy Asymptomatic bacteriuria
TMP-SMX (Cotrimoxazole) Generations • Need treatment (may progress to Pyelonephritis)
st rd
Trimethoprim + Sulfamethoxazole (Cotrimoxazole) 1 Generation 3 Generation Associated with
Sequential blocking in DNA formation sequence (Norfloxacin) • ↑ rate of Preterm labour
• Marked enhancement (synergism) of the activity of both • Premature delivery
drugs • ↓ Birth weight infants
• Bactericidal Relatively safe
Adverse Effects • Ampicillin, Amoxycillin
Fever • Cephalosporins (Cefalexin, Cefaclor)
Rash Retain Gram –ve ac tivity Avoid
Nausea ↓ often used today Improved activity against • Co-trimoxazole, Trimethoprim (Teratogenicity)
Vomiting Moderate Gram –v e activity atypical, Gram +ve • Gentamicin (Fetal Ototoxicity)
Stev en-Johnson Syndrome Minimal Serum concentration • Tetracycline (Teeth discoloration, Interfere fetal bone growth)
Actions of Sulfonamides, Trimethoprim Treat uncomplicated UTI • Quinolones (Fetal Arthropathy)
nd th
2 Generation 4 Generation Treatment – 7-10 days
(Ciprofloxacin, Levofloxacin,
Pefloxacin)

Aminopenicillin ↑ activity than

Expanded Gram –ve activity
Some Gram +ve, Atypical
Mycoplasma pneumoniae
Chlamydia pneumoniae
Excreted via Renal Route
penicillin
(can penetrate Gram –ve outer
Improved Gram +ve coverage membrane)
Maintain Gram –ve activity
Gains Anaerobic coverage
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Drugs used in STD

Macrolides Cephalosporin Antivirals
Penicillin Doxycycline Metronidazole
Azithromycin, Erythromycin Ceftriaxone, Cefixime Acyclovir, Famciclovir, Valacyclovir Antiretroviral
Penicillin Inhibit protein synthesis Chancroid (H. ducreyi) Tetracycline group MOA Active against Herp es Virus family Reverse Transcriptase Inhibitors
Penicillin V Penicillin G Excretion via bile Gonorrhea (Gonnococcus) Broad spectrum React with Intracellular MOA Nucleoside Non
(Oral) (Parenteral) Treatment of choice for Chancroid Bacteriostatic against macromolecules Interferes with viral DNA replication RTI Nucleoside
Benzathine (H. ducreyi) Gram +v e Active against Effective in RTI
Aqueous Gonorrhea – combine with Gram –v e Anaerobe ↓ Viral Shedding Zidovudine Nevirapine
Procaine cephalosporin or quinolone Rickettsiae Protozoa ↓ Duration of symptoms (AZT)
Crystalline Lymphogranuloma Venerium Chlamydiae Drug of choice in Maximum benefit if start early Didanosine Efavirenz
nd Mycoplasmas
Treatment of choice for Syphilis (Clamydia trachomatis) 2 choice Bacterial Vaginosis Uses Lamivudine
Some Protozoa Trichomoniasis 1°, Recurrent Genital Herp es (3TC)
1°, 2° Syphilis MOA Inhibit Protein synthesis Herpes zoster (require ↑ dose)
Single dose IM Bind to 50s subunit Good at GIT absorption (varicella zoster ↓ susceptible Protease Inhibitors
Benzathine Penicillin Inhibiting Translocation ↓ with Antacids than herpes simplex) Saquinavir, Indinavir, Ritonavir
(IV in immunocompromised) Inhibit aspartyl transferase
3° Syphilis Excreted in Bile Side Effects (enzyme that cleaves individual viral
st
Weekly doses IM (3 doses) 1 choice in Lymphogranuloma GIT Upset components from large protein
Benzathine Penicillin venerium Headache precursors)
Neurosyphilis Side Effects Advantages
Procaine Penicillin (14 days) Teeth Staining (Children) Extend asymptomatic period
Allergy GIT upset ↓ Frequency of opportunistic illness
Desensitization – gradually ↑ Dose Improve survival rates
Doxycycline, Tetracycline ↓ Vertical transmission
Indication
AIDS symptoms
Asymptomatic – CD4 count
• US guideline - <200/mm3
• UK guideline - < 250/mm3
Pregnant lady with HIV infection
Baby born to HIV mother
Infants with HIV infection
Strategies for Treatment
Hit – Hard, Early
Combination Therapy – Triple drugs
Good Pretreatment assessment

Summary
Syphilis Gonorrhoea Chanchroid Chlamydia Viruses HIV
(Neisseria (Haemophilus trachomatis
gonorrhoeae) ducreyi)
st
1°, 2°, Early Latent Manifest as 1 line Lymphogranuloma Herpes Simplex NRTI (Nucleotide or
IM Penicillin G Cervicitis Ceftriaxone venerum Acyclovir Nucleoside reverse
Benzathine Urethritis Co-trimoxazole Doxycycline transcriptase
Doxycycline Proctitis Azithromycin inhibitor)
Conjunctivitis Cotrimoxazole Hepatitis PI (Protease Inhibitor)
nd
Neurosyphilis 2 line Interferon alfa NNRTI
IV Aqueous Penicillin st Ciprofloxacin (NonNucleoside
1 line
G crystalline rd Revers e Transcriptase
3 Generation
(4 hourly) Cephalosporins Inhibitors)
Trachoma
IM Aqueous Penicillin (ceftriaxone, rd
3 line Azithromycin
G Procaine + Oral cefixime)
Sulfonamides Doxycycline
Probenecid (daily) Fluoroquinolones
Doxycycline Non Specific
(ciprofloxacin,
levofloxacin) Urethritis, Cervicitis
nd
2 line Azithromycin
Cefoxitin Doxycycline
Doxycycline Levofloxacin
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Urinary Tract Defence Mechanism Quinol ones (Generations)

Micturation 1st 2nd 3rd 4th
Flush out bacteria Norfloxacin Ciprofloxaci n Clinafloxacin Moxifloxa cin*
Effective if free flow, ↓ Active against Enoxacin Sparfloxacin* Trovafloxacin*
complete evacuation Gram –ve, +ve Levofloxacin Improve activity Enhanced activity
Only for UTI use Pefloxacin Gram +ve Gram +ve
Male have longer Antibacterial
Excellent Anaerobes
urethra than Female elements in urine
Gram –ve
Organic acid (↓pH)
Antimicrobial Urea (↑ osmolality) Moderate→Good
substance se creted Gram +ve
by Prostate IgA, Glycoproteins Ciprofloxaci n
Actively secreted into (also effective
Vesico-ureteric urine against
sphincter (prevent bacteria Pseudomonas
from binding to aeruginosa)
Peristalsis of ureter uroendothelial cells) (* = Not Excreted via Renal Route)
Predisposi ng Factor Epidemiology
Age 1-50 y/o < 1y/o >50 y/o Antibiotic Sites of Action
Female Women Male Infants Male
Pregnancy Congenital Prostatic
Instrumentation structural obstruction
Urinary Tract Obstruction abnormality
Neurological dysfunction Urethral
Renal disease instrumentation
Diabetes Mellitus Incomplete
Use of spermicidal jelly bladder
emptying

Pathogenesis
Most common pathway – Ascending route
Haematogenous – Bacteremia in Chronically ill patients, Immunosuppressives
Host Factors Renal Involvement Cystitis
(Pyelonephritis)
Organism factor Ascending infection Retrograde infection
(Eg. adhesins) Vesico-ureteric-reflux into bladder
Bind to Urinary Tract Cystitis or Anatomical Colonization of
α, β Haemolysin defects intestinal bacteria in
(lysis of urinary tract ↓ Ureteric peristalsis vestibule
cells, K-antigen Pregnancy
production (form Ureteric obstruction
biofilm – resistant to Gram –ve bacterial
immune system, endotoxins
antibiotics) in E-coli