Drug Therapy of Urinary Tract Infections

What drugs should you use in infants when treating at UTI?

- Ampicillin and gentamycin are recommended to treat infants with UTI. - Nitrofurantoin is contraindicated in infants less than one month of age. - Trimethoprim/sulfamethoxazole should also be avoided in the early stages of infancy.

Is Nitrofurantoin safe in pregnancy?

- Data is conflicting. - BUT, because of the possibility of hemolytic anemia, the drug is contraindicated in pregnant patients at term (38-42 weeks of gestation). - Until more is known, it seems prudent to use alternate antibiotics when needed during any gestational age.

First-Line Drugs for Complicated Urinary Tract Infections and Acute Uncomplicated Pyelonephritis: (drugs, dosages and duration)

- Trimethoprim/sulfamethoxazole 160/800 mg bid for 14 days - Ciprofloxacin 500 mg bid for 5-7 days - Levofloxacin750 mg qd for 5-7 days

First-Line Drugs for Complicated Urinary Tract Infections: (drugs, dosages and duration)

- Trimethoprim/sulfamethoxazole 160/800 mg bid for 7-14 days - Ciprofloxacin500 mg bid for 5-14 days - Levofloxacin750 mg qd for 5-14 days - Amoxicillin (with clavulanic acid) 500 mg tid for 7-14 days - Cephalexin500 mg tid for 7-14 days

First-Line Drugs for Prophylaxis of Recurrent Infections: (drugs, dosages, and duration)

- Trimethoprim/sulfamethoxazole 40/200 mg hs 3 times a week for 6 months - Trimethoprim 100 mg hs for 6 months - Nitrofurantoin 50-100 mg hs for 6 months

First-Line Drugs for Acute Cystitis: (drugs, dosages and duration)

-Trimethoprim/sulfamethoxazole 160/800 mg bid for 3 days - Nitrofurantoin (monohydrate/macrocrystals) 100 mg bid for 5 days - Fosfomycin 3 g once 1 dayAcute CystitisFirst-Line Drugs

Clinical manifestations are dysuria, urinary urgency, urinary frequency, suprapubic discomfort, pyuria, and bacteriuria (more than **** bacteria per milliliter of urine).

100,000 (note this is important when interpreting urine cultures, but isn't so important to memorize for now)

UTIs are referred to as complicated or uncomplicated. Which of these are associated with some predisposing factor, such as calculi, prostatic hypertrophy, an indwelling catheter, or an impediment to the flow of urine (e.g., physical obstruction)?

Complicated

How can you educate patients on how to minimize GI disturbances associated with Nitrofurantoin?

GI side effects can be minimized by administering nitrofurantoin with milk or with meals

How is severe pyelonephritis treated?

Hospitalization and intravenous antibiotics.

Acute bacterial prostatitis:

Defined as inflammation of the prostate caused by local bacterial infection.

Most (more than 80%) uncomplicated, community-associated UTIs are caused by what bacterium?

Escherichia coli

True or False: Single-dose therapy is preferred over short-course due to fewer side effects

False. As a rule, short-course therapy is more effective than single-dose therapy and hence is generally preferred. (In clinical practice, single-dose is almost never used)

True or False: Severe pyelonephritis can now be treated outpatient with the development of stronger antibiotics.

False. Severe pyelonephritis, requires intravenous therapy in a hospital.

Clinical manifestations of acute uncomplicated pyelonephritis:

Fever, chills, severe flank pain, dysuria, urinary frequency, urinary urgency, pyuria, and usually bacteriuria (more than 100,000 bacteria per milliliter of urine). E. coli is the causative organism in 90% of initial community-associated infections.

In communities where resistance to these drugs exceeds 20%, which drug/drug class are good alternatives for uncomplicated cystitis?

Fluoroquinolones (e.g., ciprofloxacin)

Preferred treatment (drug) options for acute uncomplicated pyelonephritis:

Fluoroquinolones or trimethoprim/sulfamethoxazole.

When adherence is a concern, which drug is a good choice for the treatment of uncomplicated cystitis?

Fosfomycin, which requires just one dose. (this is expensive!)

Acute bacterial prostatitis causative organism:

In most cases (80%), E. coli is the causative organism.

Methenamine

Methenamine (Hiprex, Urex) is a prodrug that, under acidic conditions, breaks down into ammonia and formaldehyde. The formaldehyde denatures bacterial proteins, causing cell death. For formaldehyde to be released, the urine must be acidic (pH 5.5 or less). Because formaldehyde is not formed at physiologic systemic pH, methenamine is devoid of systemic toxicity.

Use of Methenamine:

Methenamine is used for chronic infection of the lower urinary tract. However, trimethoprim/sulfamethoxazole is preferred. Methenamine is not active against upper tract infections because there is insufficient time for formaldehyde to form as the drug passes through. Methenamine does not prevent UTIs associated with catheters.

Examples of urinary tract antiseptics:

Nitrofurantoin and methenamine.

Recurrent UTI: Reinfection

Reinfection is caused by colonization with a new organism. (more common)

Recurrent UTI: Replase

Relapse is caused by recolonization with the same organism responsible for the initial infection.

What makes urinary tract antiseptics unique?

These drugs become concentrated in the urine and are active against the common urinary tract pathogens. * Therapeutic levels are achieved only in urine. * Neither drug achieves effective antibacterial concentrations in blood or tissues. Nitrofurantoin is a first-choice drug for uncomplicated cystitis.

How long should you treat someone with antibiotics for acute uncomplicated pyelonephritis?

Treatment should last 7 to 14 days

Treatment of severe infection bacterial prostatitis with vancomycin-sensitive E. faecalis:

Treatment starts with intravenous ampicillin/sulbactam, followed by 2 to 4 weeks with oral (PO) amoxicillin, levofloxacin, or doxycycline.

For uncomplicated cystitis, which two drugs are considered the drugs of first choice

Trimethoprim/sulfamethoxazole and nitrofurantoin

True or False: Acute cystitis is a lower UTI that occurs most often in women of childbearing age.

True

True or False: Nitrofurantoin is active against a large number of gram-positive and gram-negative bacteria.

True

True or False: Conventional therapy is indicated for all patients who do not meet the criteria for short-course therapy. Among these are males, children, pregnant women, and women with suspected upper tract involvement.

True.

Single-dose therapy and short-course therapy for UTIs are recommended only for what classification of UTIs?

Uncomplicated, community-associated infections in women who are not pregnant and whose symptoms began less than 7 days before starting treatment.

Susceptibility of Methenamine:

Virtually all bacteria are susceptible to formaldehyde; there is no resistance. Certain bacteria (e.g., Proteus species) can elevate urinary pH (by splitting urea to form ammonia). Because formaldehyde is not released under alkaline conditions, infections with urea-splitting organisms are often unresponsive.

After how many UTIs per year should you consider long-term prophylaxis treatment?

When reinfections are frequent (three or more a year), long-term prophylaxis may be indicated.

Treatment of severe infection bacterial prostatitis with E. coli:

with an intravenous agent (a fluoroquinolone [e.g., ciprofloxacin]), followed by 2 to 4 weeks with an oral agent (either doxycycline or a fluoroquinolone).

Acute uncomplicated pyelonephritis is an infection of the ____?

kidneys

UTIs can be classified according to their location, in either the lower urinary tract (bladder and urethra) or upper urinary tract (kidney). Within this classification scheme, cystitis and urethritis are considered lower tract infections, whereas _____ is considered an upper tract infection.

pyelonephritis