Urinary Tract Infection

Pharmacotherapeutics of UTI

1. Dr. V. S. Swathi Assistant Professor URINARY TRACT INFECTIONS

2. Definition Urinary tract infection generally refers to presence of organism in the urinary tract together with symptoms , sometimes signs of inflammation

3. Epidemiology 150 million people are affected with UTI per year in the world. In India, 3-24% are people are suffering with UTI.

4. Types Significant Bacteriuria : It is defined as the presence of at least 1, 00, 000 bacteria/ ml of urine Asymptamatic Bacteuria : It is defined as significant bacteriuria in the absence of symptoms in patient Cystitis : A syndrome of frequency, dysuria and urgency, which usually suggests infection restricted to lower urinary tract that is, the bladder and urethra Urethral Syndrome : A syndrome of frequency and dysuria in the absence of significant bacteriuria with a conventional pathogen

5. Acute Pyelonephritis : Acute infection of one or both kidneys Chronic Pyelonephritis : It refers to continuous excretion of bacteria from the kidney to frequent recurring infection of renal tissue/ to a particular type of pathology of kidney seen microscopically/ by radiographic imaging, which may/ may not be due to infection Relapse : Reoccurrence of UTI by same organism which caused original infection Reinfection : Reoccurance of UTI by different organism

6. Risk factors Community settings Young sexually active women Structural abnormalities related to urinary tract like congenital anomalies, neurogenic bladder and obstructive uropathy Patients on prolonged use of catheters Children Elders Delayed bladder emptying Using public toilets

7. Etiology E. coli Klebsiella Proteus Staphylococcus Pseudomonas aureginosa Enterobacter Serratia Anaerobic bacteria Fungi

8. Pathogenesis Kidneys - Infection of renal parenchyma and inflammatory responses (Pyelonephritis ) ↑ Ureter - Ascending of microbes towards kidney after colonisation (Ascension) ↑ Urinary bladder - Microbial epithelial cell attachment and penetration with the help of Fimbriae (Uroepithelial Penetration) ↑ Urethra - Colonisation of microbes at periurethral area and ascends through the urethra upwards to the bladder (Colonisation) Kidneys- Infection of renal parenchyma and inflammatory responses (Pyelonephritis) ↑ Ureter- Ascending of microbes towards kidney after colonisation (Ascension) ↑ Urinary bladder- Microbial epithelial cell attachment and penetration with the help of Fimbriae (Uroepithelial Penetration) ↑ Urethra- Colonisation of microbes at periurethral area and ascends through the urethra upwards to the bladder (Colonisation)

9. Clinical Presentation Infants Failure to thrive Vomiting Diarrheoa Apathy Fever Children Increased frequency of urination Dysuria Haematuria Abdominal pain Vomiting

10. Adults Lower UTI Increased frequency of urination Dysuria Urgency Hematuria   Upper UTI (Pyelonephritis)   Increased frequency of urination Dysuria Urgency Hematuria Fever Malaise Rigor Loin pain

11. Elders Increased frequency of urination Dysuria Incontinence Hesistance

12. Complications Bacteremia Septic Shock Prostatic abscess Epididymitis Seminal vesiculitis Pyelonephritis Fistula formation Hydropyelonephrosis

13. Diagnosis Urine microscopy and culture Successful laboratory diagnosis of UTI lies in obtaining an uncontaminated urine sample Contaminating bacteria can arise from skin, vaginal flora and penis flora Patients should be instructed about collection of midstream urine sample (MUS) Before collection careful cleaning of external genitilia is compulsory 20ml of urine from only mid portion of the stream is collected, the initial and final components of urine must be void in to the toilet or bed pan For very young children special pads are available for urine collection Occasionally suprapubic aspiration directly from the bladder is done in case of unconscious patients Specimens must be reach to lab within 1-2 hours and should be refrigerated otherwise bacteria may multiply and gives false results Dipstick method is useful for rapid diagnosis of urinary blood, protein, nitrites and leukocyte estarases By microscopic method, we can identify number of RBC and WBC in urine By culture method, we can identify type of organism in urine

14. Non Pharmacological Treatment Drink plenty of water Clean external genitilia after urination Empty the bladder when it is filled and do not stop to urinate when it is filled Change catheters for every 2 weeks

15. Treatment algorithm

16. Drugs used in treatment of Urinary tract infections Drug Category Mode of action Dose Adverse effects Amoxicillin Pencillin Inhibit bacterial cell wall synthesis 250-500mg-TID (oral)-Lower UTI Nausea Diarrhoea Allergy GI disturbances Anemia Co- Amoxiclav Pencillin+ Betalactamase inhibitor Inhibit bacterial cell wall synthesis+ Prevent resistance to pencillin 375-625mg-TID(oral)-Lower UTI or 1.2g-TID (parentral) Nausea Diarrhoea Allergy GI disturbances Anemia Cefalexin Cephalosporin Inhibit bacterial cell wall synthesis 250-500mg-QID-Lower UTI Abdominal pain Anemia Angioedema Transaminitis Psedomembranous colitis

17. Cefuroxime Cephalosporin Inhibit bacterial cell wall synthesis 750mg-TID (parentral)-Pyelonephritis Diarrheoa Anemia Eosinophilia Vaginitis Transaminitis Trimethoprim Sulphonamide Inhibit folic acid synthesis 200mg-BD-Lower UTI Nausea Pruritis Photosensitivity Nephrotoxicity Hepatotoxicity Nitrofurantoin Miscellaneous Inhibit bacterial cell wall synthesis 50mg-QID(oral)-Lower UTI Nausea Neuropathy Allergy Pulmonary fibrosis Cough

18. Gentamycin Aminoglycosides Inhibit bacterial protein synthesis 80-120mg-TID Nephrotoxicity Ototoxicity Ataxia Edema Erythema Ciprofloxacin Fluroquinolone Inhibit bacterial protein synthesis 100-500mg-BD(oral)-Lower UTI or 200-400mg-BD(parentral)-Pyelonephritis Rash Pruritis Tendinitis Hepatotoxicity GI disturbances Meropenam Carbapenams Inhibit bacterial cell wall synthesis 500mg-TID(parentral)-Pyelonephritis Constipation Diarrhea Nausea Rash Convulsions Pipercilln + Tazobactum Pencillin+ Betalactamase inhibitor Inhibit bacterial cell wall synthesis+ Prevent resistance to pencillin 4.5g-TID(parentral)-Pyelonephritis) Constipation Diarrhea Nausea Rash Insomnia

19. Resources https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345309/?report=reader http://www.ijmm.org/temp/IndianJMedMicrobiol343398-4126428_112744.pdf https://reader.elsevier.com/reader/sd/pii/S1876034115001859?token=9317E54A5516A7AB4D461DB4EF9B06237A1FD4C05C531AB2216F1F1A47B5B593F8C61E0FFCA520EC86E120468F8E43B4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488331/pdf/pone.0130777.pdf http://www.ijmm.org/temp/IndianJMedMicrobiol332282-4156949_113249.pdf