Urinary Tract Infections: Outline
Urinary Tract Infections: Outline
Urinary Tract Infections: Outline
Hickling MD, FRCSC
University of Ottawa
URINARY TRACT INFECTIONS
Outline
• Definitions and Classification
• Epidemiology
• Pathogenesis
• Treatment
• Prophylaxis
• Weird and Wonderful UTIs
Definitions
• Urinary Tract Infection
– Symptomatic urothelial inflammation secondary to bacterial
adhesion and internalization within the urinary tract
• Symptoms: frequency, urgency, dysuria, suprapubic pain/pressure,
fever, flank pain
• Positive urine culture: >105 cfu/ml or >102 cfu/ml
VS.
• Asymptomatic Bacteriuria
– 2 consecutive midstream urine specimens with isolation of the
same bacterial strain in quantitative counts ≥ 105
– ABSENCE OF SYMPTOMS
UTI Classification
• Anatomical
– Lower: bladder &/or urethra “CYSTITIS”
– Upper: kidneys &/or ureters “PYELONEPHRITIS”
• Degree of Complexity
– Uncomplicated
• Healthy individuals with no structural or functional
abnormality
– Complicated
Complicated UTI
General Urological
Male Gender Nosocomial Urinary Tract Infection
Children Foreign Body
Diabetes Mellitus Indwelling catheter or Renal/Bladder
Calculi
Renal Insufficiency
Anatomical Abnormalities
Immunosuppression
Polycystic or Medullary sponge kidney
Pregnancy
Diverticuli
Neurologic disease or injury
Vesicoureteric reflux
Ureteral or urethral obstruction
Renal artery stenosis or thrombosis
Voiding Dysfunction
Surgery of the Urinary Tract
Antimicrobial Resistance
UTI Classification
• Recurrent (vs. Sporadic)
≥ 3 culture proven infections within 12 months or 2
culture proven infections within 6 months
– Reinfection: different infecting uropathogen,
negative culture between infections or infection
occurs > 2 weeks after successful treatment
– Persistence: recurrence within 2 weeks of
treatment and identical uropathogen
Outline
• Definitions and Classification
• Epidemiology
• Pathogenesis
• Treatment
• Prophylaxis
• Weird and Wonderful UTIs
Epidemiology of UTI
• Most common human bacterial infection
• >8 million outpatient visits / year and
>200,000 hospitalizations / year
Schappert, 1997
• Direct and indirect costs ~ 3.5 billion/year
Foxman, 2010
Epidemiology of UTI
Najar et al. 2009
Epidemiology of UTI
Female UTI
• Foxman et al. 2000
– 2000 women
– 10.8% (95% CI 9.4‐12.1) self‐reported UTI in past 12
months
– Extrapolated lifetime prevalence 60.4%
• NHANES III
– Incidence 13,320 cases per 100,000 women
– Lifetime prevalence 53, 067 per 100,000 women
Epidemiology of UTI
Male UTI
• 20% of all UTI
• NHANES III
– Lifetime prevalence 13, 689 per 100,000 men
• Increases with age
– BPH
– Detrusor underactivity
Bacteriology
Conclusions
almost all women with
typical UTI symptoms and
negative culture still have
an infection with E. coli
Epidemiology of rUTI
• UTI recurrence is common
– 20% college aged women had at least 1 culture confirmed UTI within 6
months1
– 179 women followed for 1 year after index E.coli infection
• 44% had at least one recurrence
• 5% had > 3 UTIs2
– Natural history of recurrence
• Cluster within the first 3‐4 months
• Most likely time 30‐60 days
• Frequency of recurrence declines with time3
1. Foxman et al. 2000
2. Ikaheimo et al. 1996
3. Stamm et al.. 1991
Epidemiology of rUTI
• Nosocomial UTI
– 80% occur in catheterized patient
– By 2 weeks 100% colonization
• 10‐25% risk of symptomatic infection
• 1‐5% risk of progressing to bacteremia
Saint S. Am J Infect Control 2000
Outline
• Definitions and Classification
• Epidemiology
• Pathogenesis
• Treatment
• Prophylaxis
• Weird and Wonderful UTIs
UTI Pathogenesis
Nielubowicz GR and Mobley HL. Host‐
pathogen interactions in urinary tract
infection. Nat Rev Urol. 2010; 7(8): 430.
UTI Pathogenesis:
Host Factors
• Genetic factors
– Positive female family history strongly predictive of UTI
– Greater binding of uropathogenic coliforms
• ABH blood group non‐secretor status
• P1 status
– Alterations in HSPA1B, CXCR1&2, TLR2&4 and TGF‐β1 genes
– Alternations in toll‐like receptors, anti‐microbial peptides (defensins and cathelicidin), anti‐bacterial
adherence factors (eg. Tamm‐Horsfall protein) and growth factors (eg. TGF‐β1 and VEGF)
• Behavioral factors
– Sexual intercourse
– Spermicide use
– Recent antibiotic use
•
• Anatomic Variations
– females: perineal and urethral anatomy are important ONLY in absence of other risk factors
– obstructed urine flow:
• medullary sponge kidney, calyceal diverticula, ureteral obstruction, ureteropelvic junction
obstruction vesicoureteric reflux, bladder outlet obstruction (primary bladder neck, urethral
stricture, or benign prostatic hyperplasia)
UTI Pathogenesis:
Host Factors
• Physiologic Factors
– Diabetes mellitus
• 1.2‐2.2 fold increased risk
• Theories: hyperglycosuria, increased glycosylation of uroplakin Ia, less effective urinary
glycoproteins and impaired bladder contractility and emptying (diabetic cystopathy)
– Pregnancy
• Prevalence of bacteriuria is similar to non‐gravid females
• However, 22‐35% progression to pyelonephritis
– Secondary to hydronephrosis of pregnancy
– Dysfunctional voiding
– Neurologic diseases
• Detrusor‐external sphincter dyssynergia
– Postmenopausal Female
• Atrophic vaginitis
– Decreased levels of lactobacilli, antimicrobial peptides
• Incontinence
• Cystocele
• Elevated post‐void residual
UTI Pathogenesis:
Bacterial Factors
• Pathogenicity islands
– Large DNA blocks encoding virulence factors
– Disseminate b/w distinct strains
• Virulence factors
– Adhesins: Fim‐H, P‐pili
– Toxins: hemolysin
– Proteases
– Invasins
– Serum resistance factors
– Motility mediators
– Iron acquistion systems
– Acid polysaccharide capsule
• Biofilm Min et al. 2006
UTI Pathogenesis: Biofilm
• deposition of a “conditioning layer” of
reactive host proteins
• adhesin‐mediated microorganism
attachment
• microorganisms change phenotypically
– produce exopolysaccharides
• Secure microorganisms to the catheter
surface
• protected against exogenous
antimicrobials and innate host defenses
• Formation of organized microcolonies
– shed daughter cells and biofilm
aggregates seeding other sections of
the catheter and urinary tract.
UTI Pathogenesis
• Routes of infection:
– Ascending (majority)
• From extra urinary sources such as the distal gut or vaginal
epithelium (majority)
– Hematogenous (rare)
• Increased with ureteral obstruction
• Staphylococcus bacteremia or Candidal fungemia
– Quiescent intracellular reservoirs
• Dormant uropathogenic bacteria residing within urothelial
cells
• Evade host immune responses and can emerge at any given
time to reinfect host
UTI Pathogenesis
Kaper et al. Nature Reviews Microbiology 2004
Intracellular Bacterial Communities
Dhakal BK et al. 2008
rUTI Pathogenesis
O’Brien VP. et al. Nat Microbiol. 2016
Diagnosis
History and Physical Exam
Laboratory Testing
• Urinalysis
– Leukocyte esterase
• Sensitivity 68‐98% and Specificity 59‐96%
• Positive predictive value 19‐86% and Negative predictive value 91‐97%
– Nitrite
• Sensitivity 19‐45% and Specificity 95‐98%
• Positive predictive value 50‐78% and Negative predictive value 82‐89%
– Leukocyte esterase and Nitrite
• Sensitivity 35‐84% and Specificity 98‐100%
• Positive predictive value 84% and Negative predictive value 98%
•
• Microscopy
– Bacterial counts >30,000 cfu/ml for detection
– ≥ 1 bacteria per hpf (uncentrifuged urine) correlates to ≥ 105 cfu/ml via culture
– Pyuria: ≥ 10 WBCs/hpf
Diagnosis
Laboratory Testing con’t
• Urine culture and sensitivities (Gold Standard)
• Obtain prior to initiation of empiric therapy if:
– atypical symptoms
– negative urinalysis
– recent antibiotic use,
– Complicated
• ≥ 105 cfu/ml urine is the classic definition of a positive urine culture
• ≥102 cfu/ml urine can be used for UTI diagnosis in a symptomatic patient
Diagnosis
Additional urologic investigation
• upper tract imaging, cystoscopy, urodynamics
• generally unnecessary during initial diagnostic testing
• Indications
– Complicated UTI
– persistent fever (72 hours after initiation of treatment)
– suspected urolithiasis (urine pH ≥ 8.0, history of calculi)
– unexplained/persistent hematuria
– bacterial persistence
– analgesic abuse
– urinary retention
Outline
• Definitions and Classification
• Epidemiology
• Pathogenesis
• Treatment
• Prophylaxis
• Weird and Wonderful UTIs
Treatment:
Antimicrobial Resistance
MAJOR threat to public health
CDC 2013/WHO 2014
Approaching a post‐antibiotic age
Davies and Davies 2010
CDC 2013
Treatment:
Antimicrobial Resistance
CDC 2013
Treatment:
Antimicrobial Resistance
http://www.reactgroup.org/
Treatment: Acute UTI
RESULTS
Pilot study = NON‐INFERIORTY
2/3 treated with ibuprofen had
complete resolution without
antibiotics and less recurrence
HOWEVER
‐ Higher rate of pyelonephritis
‐ 1 episode GI hemorrhage
Bleidorn et al. BMC Medicine 2010
Gágyor et al. BMJ 2015
Treatment: Acute UTI
• Individualized to patient and
local community resistance
prevalence
• Suspect complicated UTI
– urine specimen prior to
treatment
– treatment duration should be
adjusted to 10‐14 days
• Signs of urosepsis
– broad spectrum intravenous
antimicrobials such as 2nd or 3rd
generation cephalosporins
– consider urinary tract imaging
Gupta et al. 2011
Antimicrobial Agents
in Urology
• Testable!
– Mechanism of action
– Spectrum of activity
– Side effects
– Contraindications
– Antimicrobials in Pregnancy
• Potential side effects applicable to all
– Allergic reaction, hypersensitivity, rash, yeast
infection, GI upset, pseudomembranous colitis
Outline
• Definitions and Classification
• Epidemiology
• Pathogenesis
• Treatment
• Prophylaxis
• Weird and Wonderful UTIs
Antimicrobial Prophylaxis
• Standards
– Antimicrobial administration
• Guidelines
– Asymptomatic bacteriuria
– Genitourinary procedures
– Endocarditis
• AUA Best Practices
– Joint replacements
– Prostate biopsy
– Genitourinary prostheses
• Recurrent UTI
Antimicrobial Prophylaxis
Standard
• < 1 hour prior to incision
– 2 hours if vancomycin
• OR attending to document if patient not
eligible
Antimicrobial Prophylaxis
Guidelines
Asymptomatic bacteriuria
IPE, 2013
Antimicrobial Prophylaxis
IDSA Guidelines
Asymptomatic bacteriuria
– Screening and treatment indicated in two
populations
• Pregnant women
– 20‐30x higher risk of pyelonephritis
» Pre‐term labor and low birth weight
– Screening to begin 12‐16 weeks
• Urologic procedures
– If mucosal bleeding anticipated
» Eg. TURP, TURBT, Ureteroscopy
Gupta et al. 2011
Antimicrobial Prophylaxis
AHA Guidelines
Infective endocarditis
– American Heart Association
• Infective endocarditis is much more likely from
random bacteremias associated with daily activities
• Therefore endocarditis prophylaxis not recommended
for GU procedures
Wilson et al. Circulation. 2007
Antimicrobial Prophylaxis
AUA Best Practice
• Total Joint Replacements
– Prophylaxis NOT indicated for most healthy
urologic patients with
• Placement of pins, plates, and/or screws
• Total joint replacements
– Consider prophylaxis
• < 2 years after joint replacement
• At risk patients undergoing high risk procedures
Total Joint Replacement
Prophylaxis
At Risk Population High Risk GU Procedures
• < 2 years after joint • Stone manipulation
– NOT ESWL
replacement • Transmural incision
• Immunocompromised or • Upper endoscopy
immunosuppressed • Transrectal biopsy
• Procedure includes bowel
• Previous prosthetic joint segment
infection • Entry into urinary tract if
colonization likely
• Malnourished – Catheterization
– Stent
• Hemophilia – Recurrent UTIs
• Malignancy – Urinary diverstion
Total Joint Replacement
Prophylaxis
Suggested Regimens
• Single system quinolone dose
– Ciprofloxacin 500 mg
– Levofloxacin 500 mg
– Ofloxacin 400 mg
• Ampicillin 2g IV (or vancomycin 1 g IV) plus gentamycin 1.5
mg/kg IV
Antimicrobial Prophylaxis
AUA Best Practice
Transrectal Prostate Biopsy
– Quinolones (oral or IV)
– Aminoglycoside plus metronidazole or
clindamycin*
– Cephalosporins (1st, 2nd, 3rd generation)*
– Aztreonam plus metronidazole or clindamycin
* May be better in some communities owing to
high fluoroquinolone resistance rates
Antimicrobial Prophylaxis
AUA Best Practice
Implanted Prosthesis
Antimicrobial Prophylaxis
Recurrent UTI
Cochrane Review
Antimicrobial Prophylaxis
Recurrent UTI
AUA Update Lesson 12 2012
Non‐antimicrobial Prophylaxis
Recurrent UTI
Cranberry Extract or Juice
‐Proanthocyanidin inhibits Fim‐H binding to urothelium
‐Cranberry juice (240 ml) reduced rUTI 39%
Maki et al. Am J Clin Nutr. 2016
Vaginal Estrogen
‐restore innate immunity and lactobacilli (lower pH)
D‐mannose
‐inhibit FimH – Uroplakin Ia binding
INSUFFICIENT EVIDENCE
Methanamine salts
‐ hydrolyzed ammonia & formaldehyde
Formaldehyde = bacteriostatic
Outline
• Definitions and Classification
• Epidemiology
• Pathogenesis
• Treatment
• Prophylaxis
• Weird and Wonderful UTIs
Acute Bacterial
Prostatitis (NIH Category I)
• Rare
• Acute onset symptoms: perineal pain, irritative storage
and obstructive voiding symptoms, fever, chills, malaise
• Physical exam: boggy, hot, tender, very tender prostate
• Bacteriology
• 65‐80% E. coli
• 5‐10 % Enterococcus
• Pseudomonas, Enterobacter, Klebsiella
Acute Bacterial
Prostatitis (NIH Category I)
• Risk factors:
– UTI
– condom or indwelling catheter
– unprotected penetrative and rectal intercourse
– transurethral surgery
– prostate biopsy
– dysfunctional voiding intraprostatic ductal
reflux
• anatomic or neurophysiologic
Acute Bacterial
Prostatitis (NIH Category I)
• Diagnosis
– U/A and urine culture
– Note: expression of prostatic fluid is unnecessary and
perhaps harmful
• Treatment
• Ampicillin+gentmicin, 2nd or 3rd generation cephalosporin,
fluoroquinolone
– Duration 2‐6 weeks
• Transrectal ultrasound if not improvement within 36 hours
rule out prostate abscess
Chronic Bacterial
Prostatitis (NIH Category II)
• 5‐15% of prostatitis cases
• > 3 months
• Important clue:
– Asymptomatic between episodes (although can have CPPS)
– Recurrent UTIs
• 25‐43%
• Physical exam:
– Unremarkable with the except of pain
– DRE only after preprostatic massage urine specimens collected
Chronic Bacterial
Prostatitis (NIH Category II)
Diagnosis
Mandatory
– history & physical exam (DRE and pelvic floor)
– Urinalysis and urine culture
Recommended
– 2 glass test
– NIH‐Chronic Prostatitis Symptom Index (CPSI)
– Sexual function assessment
– Uroflow/PVR
– Urine cytology
Not Recommended for Routine Evaulation (Optional)
– Meares‐Stamey Test / 4 Glass Test
– Seimn analysis and culture
– STI testing or urethral swab
– UDS
– Transrectal U/S or pther pelvic imgaing
– PSA
Chronic Bacterial
Prostatitis (NIH Category II)
Category II diagnosed if
10‐fold increase in
bacteria in EPS or VB3
vs. VB1 and VB2
Chronic Bacterial
Prostatitis (NIH Category II)
Chronic Bacterial
Prostatitis (NIH Category II)
Treatment
Fig 13.9 Campbell’s Urology
Emphysematous
Pyelonephritis
• Urologic emergency with high mortality rate
(19‐43%)
• Acute necrotizing parenchymal and perirenal
infection by gas forming microorganisms
– E.coli > Klebsiella and Proteus
Emphysematous
Pyelonephritis
• Presentation
– Adults
– Diabetic
• Obstructed urinary tract:
calculi, papillary necrosis
– Triad: fever, vomiting and
flank pain
– Radiologic findings (how
diagnosis is established)
• CT preferred over plain film
– Streaky or mottled gas
with or without bubbly and
loculated gas
Campbell’s 11th edition
Emphysematous
Pyelonephritis
• Treatment
– Medical management
• Broad spectrum antimicrobials and fluid resuscitation
• + Catheter drainage if obstructed
• Note: ONLY if normally functioning/non‐obstructed kidney
– Nephrectomy
• Not responding to medical therapy
• Non‐function kidney
Xanthogranulomatous
Pyelonephritis
• Rare, severe, chronic renal infection with
diffuse renal destruction
– Associated with:
• Obstruction secondary to nephrolithiasis (Staghorn)
• Poor renal function
• Infection: Proteus > E.coli and ~ 10 % mixed culture
• Accumulation of lipid‐laden foamy
macrophages
Xanthogranulomatous
Pyelonephritis
• Treatment
– Stabilize the patient with antimicrobial therapy
– Nephrectomy and removal of entire inflammatory
mass
• Perinephric fat
• Diaphram
• Great vessels
• bowel
Malakoplakia
• “soft plaques”
• Originally described in bladder
– GU and GI tract, skin, lungs, bones and mesenteric LN
• Defect in intraphagosomal bacterial digestion
• Presentation: > 50 years, 4:1 female to male ratio,
immunosuppressed with other chronic diseases
Malakoplakia
• Diagnosed by biopsy
– Large histiocytes “von
Hansemann cells”
– Small basophillic, extra‐
or intracytoplasmic
calculospherules
“Michaelis‐Gutmann
bodies”
Malakoplakia
Treatment
– Long term antimicrobial therapy to eradicate
intracellular bacteria
• Sulfonamides and/or TMP
• Doxycycline
• Rifampin
• Quinolones
– Surgical intervention if disease progression
Genitourinary Tuberculosis
• Mycobacterium tuberculosis
• 2‐10% of patients with pulmonary TB in the developed world
– HIV/AIDS or foreign born
• Kidney and epididymis most common GU sites
• Renal TB progression
– Calyceal stricture/destruction
– Calcification
– Decreased blood flow
– Seeding: Ureter stricture, Bladder starts at ureteric orifice
stricutre/reflux
Genitourinary Tuberculosis
Diagnosis
– Symptoms: often minimal and/or vague
• Frequency
• Malaise, weight loss, lethargy, low‐grade temp
• Hypertension
• Painful epididymal or scrotal swelling
• Hematospermia
– Urine studies (CRITICAL)
• 3‐5 first void urine samples for acid‐fast bacilli and culture
– Done ASAP
– Culture results within 3‐4 weeks
• In future
– PCR method
– Mass spectrometry
Genitourinary Tuberculosis
Diagnosis
– PPD skin test
• Does not differentiate b/w active and latent disease
• Cannot rule out disease with negative test
• Therefore not used in GU TB
– Cystoscopy rarely indicated
– Radiology
• Plan film: punctate calcifications within parenchyma,
intraluminal in ureter
• IVU
• CT Urogram scan preferred and replaced IVU
Genitourinary Tuberculosis
Radiologic findings
– Irregular “moth‐eaten” calyces
– Hydrocalyx, hydronephrosis, hydroureter
– Superiorly displaced “hiked –up” UPJ
– Ureteral stricture
• Most common site: distal ureter
• Can be multiple
Genitourinary Tuberculosis
Treatment (CDC Guidelines)
– Medical therapy for 6 months
• First 2 months 4 antimicrobial agents: isoniazid, rifampin,
pyrazinamine, ethambutol
• Next 4 months: isoniazid and rifampin
– Surgery (nephrectomy, partial nephrectomy, ureteral
stricture, augmentation cystoplasty, epididymectomy)
• Persistent symptoms
• Extensive disease with HTN, UPJO
• Suspicious for malignancy
APPENDIX
Antimicrobial Agents
In
Urology
Ampicillin or Amoxicillin
• MoA
– Inhibit bacterial cell wall synthesis
• Spectrum
– Strep, Enterococcus, Proteus, E. coli
• Disadvantages
– 40% E.coli resistance in some areas
– Can disrupt normal vaginal flora (ie. Lactobacilli)
– Acute interstitial nephritis
Ampicillin + Clavulanate
• MoA
– Inhibits bacterial beta‐lactamase
– Less resistance
• Spectrum
– Strep, Enterococcus, Proteus, E. coli
• Disadvantages
– disrupt normal vaginal flora
– GI side effects
Vancomycin
• MoA
– Inhibits bacterial cell wall synthesis
• Spectrum
– Gm +ve including most MSRA
• Disadvantages
– Potential oto‐ or nephrotoxicity
– Nonspecific mast cell degranulation and histamine
release “Red‐man syndrome”
Extended‐Spectrum Penicillins
• Examples: piperacillin, ticarcillin, mecillinam
• MoA
– Inhibit bacterial bacterial cell wall synthesis
– Usually combined with beta‐lactamase inhibitor
• Ticarcillin/clavulanic acid
• Pip/Tazo
• Spectrum
– Variable (reference individual agents)
• Disadvantages
– Same as ampicillin/amoxicillin
– High sodium load
Cephalosporins
• MoA
– Inhibit bacterial cell wall synthesis
• Spectrum
– 1st: Strep, Staph (not MRSA), some Gm –ve
– 2nd: Strep, some Gm –ve, some anaerobes
– 3rd: Strep, most Gm –ve, some cover Pseudomonas
(Ceftazidime)
– 4th: Strep, Staph, most Gm –ve including Pseudomonas
• Disadvantages
– Similar to penicillins
– 10% cross reactivity in penicillin allergic patients
Cephalosporins
* Oral agents
Trimethoprim/Sulfamethoxazole
• MoA
– Inhibits bacterial folate metabolism
• Spectrum
– Strep, Staph, Gm –ve rods except Pseudomonas
• Disadvantages
– E. coli resistance > 20 % in some areas
– Interact with warfarin
– Affect fetal development
– Hematologic problems: AIDS, G6PD deficiency
Nitrofurantoin
• MoA
– Inhibits several bacterial enzymes
– Damages bacterial DNA
• Spectrum
– E.coli, Klebsiella, Enterococcus, Staph saprophyticus
• Disadvantages
– Neurotoxicity
– Interstitial pneumonitis
– Poor tissue penetration
– Require longer treatment
Tetracyclines
• MoA
– Inhibit ribosomes and therefore protein synthesis
• Spectrum
– Broad
– STIs
• Disadvantages
– Tooth and bone toxicity in pregnancy, childhood
– Photosensitivity
– Resistance
Fluoroquinolones
• MoA
– Inhibit bacterial DNA gyrase
• Spectrum
– Most Gm –ve including Pseudomonas
– Some Strep coverage
• Advantages
– Good tissue penetration (prostate, kidney)
Fluoroquinolones
• Disadvantages
– Drug interactions
• Warfarin
• Benzodiazepine withdrawal
– Lower seizure threshold
– Cartilage development (avoid in pregnancy)
– Tendinitis/tendon rupture
• Eg. Achilles tendon
• At risk: elderly, steroid use, transplant patients
– Clostridium difficile colitis
Aminoglycosides
• MoA
– Inhibit ribosomal protein synthesis
• Spectrum
– Most Gm –ve including Pseudomonas
• Disadvantages
– Oto‐ and nephrotoxicity
– Neuromuscular blockade (high concentration)
• Avoid in myasthenia gravis
• Contraindication to botulinum toxin use
Antimicrobial Agents in
Pregnancy
Avoid in 3rd Trimester
Sulfonamides
• Hemolytic anemia in G6PD patients
• Neonatal jaundice
Nitrofurantoin
• Hemolytic anemia due to immature
enzymes
• Also avoid in G6PD patients
Campbell’s Urology 11th ed.
Genitourinary Tuberculosis
Antimicrobial Agents
Isoniazid
– MoA
• inhibits synthesis of mycolic acids (cell wall)
• Kills rapidly dividing bacteria
– Adverse reactions:
• Liver toxicity (higher if also drink alcohol)
• Neurotoxicity (give pyridoxine supplement)
• May increase levels of phenytoin and carbamazepine
Genitourinary Tuberculosis
Antimicrobial Agents
Rifampin
– MoA
• Inhibits bacterial RNA polymerase
• Works on dividing and semi‐dormant bacteria
– Adverse reactions: uncommon
• All get orange discoloration of body fluids
– Drug interactions
• Induces cytochrome P450 enzymes
• Many drugs reduced to subtherapeutic levels, including
anti‐HIV protease inhibitors and non‐nucleoside reverse
transcriptase inhibitors
Genitourinary Tuberculosis
Antimicrobial Agents
Pyrazinamine
– MoA
• unknown
• Works on dormant and semi‐dormant bacteria
– Adverse reactions
• Arthralgias 40%
• Increase in uric acid
– Cannot use if patient has gout
– Xanthine oxidase inhibitor
Genitourinary Tuberculosis
Antimicrobial Agents
Ethambutol
– MoA
• unknown
• Works on actively dividing bacteria
– Major adverse reaction
• Retrobulbar neuritis
– Follow visual acuity and red‐green color discrimination