Drugs Used in UTI STD

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Drugs Used in UTI & STDs UTI Uncomplicated Healthy person esp women No underlying risk factor

Etiology of UTI Community Acquired Gram –ve Aerobes from GIT • E-coli • Coagulase-negative staph Enterobacteriaceae • Proteus mirabilis • Klebsiella Enterococcus faecalis

Principles of Antibacterial Therapy 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

Hospital Acquired E-coli Pseudomonas aeruginosa Proteus, Enterobacter, Serratia, Acinetobacter Staphylococcus aureus (hematogenous spread )

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 ↓ Side effects (be8 er compliance ) Suited local bacterial sensitivity patterns Easy administration – Oral, IV Duration of Treatment Considerations Type of Antibiotics used UTI is complicated/ non -complicated Uncomplicated cystitis (women) – 1 week Longer (7-14 days) Pregnancy Elderly Infant Pyelonephritis 4-6 weeks Relapse with same organism Diabetic, Polycystic Kidneys, Renal transplant

STD Bacterial Gonorrhoea

Syphilis Chancroid Nongonococcal urethritis Syphilis

Viral AIDS

Herpes genitalis Viral hepatitis

Mycoplasma Nongonococcal urethritis

Protozoal Trichomoniasis

Fungal Vaginal candidiasis

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Drugs used in UTI Sulfamethoxazole (SMX) Sulfonamide group Bacteriostatic Gram +v e, Gram –ve Chlamydia trachomatis Protozoa Enteric bacteria (E.coli, Klebsiella, Salmonella, Shingella, Enterobacter)

Adverse Effects Urticaria, Stev en-Johnson syndrome Nausea, Vomiting, Diarrhea Stomatitis, Arthritis Haemolysis (G6PD Deficiency) • Kernicterus (↑ risk newborns – taken end of pregnancy)

Trimethoprim (TMP) Bacteriostatic Concentrates in Vaginal fluids Prostate Urine st 1 line treatment & prophylaxis for UTI

Adverse Effects Megaloblastic anaemia Leukopenias (less)

Quinolones Active against Gram –v e bacteria and some gram +ve Block bacterial DNA Synthesis by Inhibiting Bacterial Topoisomerase II Topoisomerase IV (DNA Gyrase) Prevent relaxation of +vely Interfere with separation of supercoiled DNA required for replicated chromosomal DNA normal transcription & into respective daughter cells replication during division

Non Fluorinated Quinolones Nalidixic acid st 1 Quinolone Excreted too rapidly into urine (unable to achieve Systemic Antibacterial Concentration) Useful only for Lower UTI E.coli, Enterobacter, Klebsiella, Proteus Adverse Effects False +ve Glycosuria GIT Upset

Steven-Johnson Syndrome

TMP-SMX (Cotrimoxazole) Trimethoprim + Sulfamethoxazole (Cotrimoxazole) Sequential blocking in DNA formation sequence • Marked enhancement (synergism) of the activity of both drugs • Bactericidal Adverse Effects Fever Rash Nausea Vomiting Stev en-Johnson Syndrome Actions of Sulfonamides, Trimethoprim

Generations st 1 Generation (Norfloxacin)

↓ often used today Moderate Gram –v e activity Minimal Serum concentration Treat uncomplicated UTI nd 2 Generation (Ciprofloxacin, Levofloxacin, Pefloxacin)

Expanded Gram –ve activity Some Gram +ve, Atypical Mycoplasma pneumoniae Chlamydia pneumoniae Excreted via Renal Route

Fluoroquinolones Synthetic Fluorinated analog of Nalidixic acid Improved antibacterial activity (broad spectrum) Able to achieve Systemic Antibacterial concentrations ↓ Absorption with Antacids (avoid) Adverse Effects (Generally well tolerated) (Minimal adverse effec ts) Nausea Vomiting Indication • Reserv ed for complicated cases • Not responding to cotrimoxazole • Basis of Bacteriological sensitivity • Due to ↑ cost with similar efficacy

Nitrofurantoin Well absorbed Rapidly excreted into Urine • No systemic Antibacterial action achieved • Activity enhanced in ↓pH (do not alkalinize urine) • Urinary antiseptics (antibacterial activity in urine with little/no systemic effects) Excretion into Urine via GFR & Tubular secretion (in Renal Failure, ↓ Efficacy & Toxicity) Bacteriostatic, Bactericidal for many Gram +ve, Gram -ve Not effective ag ainst Pseudomonas aeruginosa & Proteus infection MOA • Unknown • Cause bacterial DNA damage (suggest) Adverse Effects Anorexia Nausea Haemolysis (G6PD Deficiency)

Ampicillin, Amoxycillin Extended spectrum Penicillin (aminopenicillin) Bactericidal for growing cells Beta Lactam Antibiotics Well absorbed (amoxycilin better absorbed) Impaired by food (take 1-2h before meal) Excreted via urine Can be given IV Gram +v e, Gram –ve cocci (able to penetrate gram –v e outer membrane unlike penicillin) Anaerobes Enterococci Listeria E.coli H. Influenza (↑ dose)

Used in Resistant UTI cases Complicated UTI Cephalexin, Cefaclor, Cefixime Treatment Prophylaxis ↑ Cost

Aminoglycosides No oral preparation (poor absorption) Parenteral Excreted unchanged via Kidney Used in in-patient treatment Affect Renal Function Gentamicin Amikacin MOA Block initiation complex Miscoded peptide chain Block Translocation

Not useful against Klebsiella Enterobacter Pseudomonas aeruginosa Indole +ve Proteus MOA Inhibition of cell wall synthesis Inhibit Transpeptidation

UTI in Pregnancy Asymptomatic bacteriuria • Need treatment (may progress to Pyelonephritis) Associated with • ↑ rate of Preterm labour • Premature delivery • ↓ Birth weight infants Relatively safe • Ampicillin, Amoxycillin • Cephalosporins (Cefalexin, Cefaclor) Avoid • Co-trimoxazole, Trimethoprim (Teratogenicity) • Gentamicin (Fetal Ototoxicity) • Tetracycline (Teeth discoloration, Interfere fetal bone growth) • Quinolones (Fetal Arthropathy) Treatment – 7-10 days

rd

3 Generation

Retain Gram –ve ac tivity Improved activity against atypical, Gram +ve

th

4 Generation

Improved Gram +ve coverage Maintain Gram –ve activity Gains Anaerobic coverage

Cephalosporins Beta Lactam Antibiotics MOA & Toxicity Similar to Penicillin ↑ Stable than Penicillins to bacterial lactamases • Broader spectrum of activity • Not useful against enterococci, listeria monocytogenes

Aminopenicillin ↑ activity than penicillin (can penetrate Gram –ve outer membrane)

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Drugs used in STD

Penicillin G (Parenteral) Benzathine Aqueous Procaine Crystalline Treatment of choice for Syphilis

Macrolides Azithromycin, Erythromycin Inhibit protein synthesis Excretion via bile Treatment of choice for Chancroid (H. ducreyi) Gonorrhea – combine with cephalosporin or quinolone Lymphogranuloma Venerium nd (Clamydia trachomatis) 2 choice

1°, 2° Syphilis Single dose IM Benzathine Penicillin

MOA Bind to 50s subunit Inhibiting Translocation

Penicillin Penicillin Penicillin V (Oral)

Cephalosporin Ceftriaxone, Cefixime Chancroid (H. ducreyi) Gonorrhea (Gonnococcus)

1°, 2°, Early Latent IM Penicillin G Benzathine Doxycycline Neurosyphilis IV Aqueous Penicillin G crystalline (4 hourly) IM Aqueous Penicillin G Procaine + Oral Probenecid (daily)

Gonorrhoea (Neisseria gonorrhoeae) Manifest as Cervicitis Urethritis Proctitis Conjunctivitis

Excreted in Bile st 1 choice in Lymphogranuloma venerium Side Effects Teeth Staining (Children) GIT upset

Chanchroid (Haemophilus ducreyi) st 1 line Ceftriaxone Co-trimoxazole

Chlamydia trachomatis Lymphogranuloma venerum Doxycycline Azithromycin Cotrimoxazole

nd

st

1 line rd 3 Generation Cephalosporins (ceftriaxone, cefixime) Fluoroquinolones (ciprofloxacin, levofloxacin) nd 2 line Cefoxitin Doxycycline

Tetracycline group Broad spectrum Bacteriostatic against Gram +v e Gram –v e Rickettsiae Chlamydiae Mycoplasmas Some Protozoa Inhibit Protein synthesis Good at GIT absorption ↓ with Antacids

3° Syphilis Weekly doses IM (3 doses) Benzathine Penicillin Neurosyphilis Procaine Penicillin (14 days) Allergy Desensitization – gradually ↑ Dose Doxycycline, Tetracycline

Summary Syphilis

Doxycycline

2 line Ciprofloxacin

rd

3 line Sulfonamides Doxycycline

Trachoma Azithromycin Doxycycline Non Specific Urethritis, Cervicitis Azithromycin Doxycycline Levofloxacin

Viruses

Herpes Simplex Acyclovir

Hepatitis Interferon alfa

HIV

NRTI (Nucleotide or Nucleoside reverse transcriptase inhibitor) PI (Protease Inhibitor) NNRTI (NonNucleoside Revers e Transcriptase Inhibitors)

Metronidazole MOA React with Intracellular macromolecules Active against Anaerobe Protozoa Drug of choice in Bacterial Vaginosis Trichomoniasis

Antivirals Acyclovir, Famciclovir, Valacyclovir Antiretroviral Active against Herp es Virus family Reverse Transcriptase Inhibitors MOA Nucleoside Non Interferes with viral DNA replication RTI Nucleoside RTI Effective in ↓ Viral Shedding Zidovudine Nevirapine (AZT) ↓ Duration of symptoms Didanosine Efavirenz Maximum benefit if start early Lamivudine Uses (3TC) 1°, Recurrent Genital Herp es Herpes zoster (require ↑ dose) (varicella zoster ↓ susceptible Protease Inhibitors than herpes simplex) Saquinavir, Indinavir, Ritonavir (IV in immunocompromised) Inhibit aspartyl transferase Side Effects (enzyme that cleaves individual viral GIT Upset components from large protein Headache precursors) Advantages Extend asymptomatic period ↓ Frequency of opportunistic illness Improve survival rates ↓ Vertical transmission Indication AIDS symptoms Asymptomatic – CD4 count • US guideline - 50 y/o Male Prostatic obstruction Urethral instrumentation Incomplete 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

Quinol ones (Generations) 1st 2nd Norfloxacin Ciprofloxaci n ↓ Active against Enoxacin Gram –ve, +ve Levofloxacin Only for UTI use Pefloxacin Excellent Gram –ve Moderate→Good Gram +ve Ciprofloxaci n (also effective against Pseudomonas aeruginosa)

3rd Clinafloxacin Sparfloxacin* Improve activity Gram +ve

4th Moxifloxa cin* Trovafloxacin* Enhanced activity Gram +ve Anaerobes

(* = Not Excreted via Renal Route) Antibiotic Sites of Action