Course

Antibiotic Use in UTI

Course Highlights


  • In this Antibiotic Use in UTI course, we will learn about differentiating between uncomplicated and complicated UTIs.
  • You’ll also learn to differentiate between the classes of antibiotics and their mechanism of action. 
  • You’ll leave this course with a broader understanding of key considerations when prescribing antibiotics for UTI.

About

Pharmacology Contact Hours Awarded:

Course By:
Amanda Marten

MSN, FNP-C

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The following course content

Introduction   

A urinary tract infection (UTI) can develop in anyone but is more common in females than males. Approximately 40% of American women will develop a urinary tract infection in their lives [2]. Many UTIs can lead to serious health complications, including sepsis and sometimes patient mortality.  

Thus, healthcare providers must be knowledgeable of the signs and symptoms of UTIs, the available antibiotics, and UTI treatment guidelines. Understanding the different pharmacokinetics of antibiotics used to treat UTIs is essential during drug selection. This course outlines UTI antibiotic pharmacology and addresses pharmacokinetics, including mechanism of action, side effects, usage, and contraindications.

Definitions 

This section covers the definitions related to UTI treatment and management. 

Urinary Tract Infection 

Bacterial infection of the lower urinary tract (usually confined to the bladder). This is also sometimes called cystitis and is primarily caused by the bacteria E. coli [2]. 

Asymptomatic Bacteremia 

A urine specimen is collected on a patient and shows the presence of bacteria, but they do not have any UTI symptoms [5]. 

Pyelonephritis 

Bacterial infection of the upper urinary tract (i.e. kidneys) [6]. 

Urosepsis 

When a urinary tract infection causes a systemic infection, also known as sepsis [6]. 

Quiz Questions

Self Quiz

Ask yourself...

  1. What is a urinary tract infection? 
  2. What is asymptomatic bacteremia? 
  3. What is pyelonephritis? 
  4. What is urosepsis? 

Medications Overview 

This section briefly reviews UTI antibiotic classes and medical indications. 

Certain antibiotics are used to prevent or treat urinary tract infections and are used in both inpatient and outpatient settings. Healthcare providers should follow current guidelines regarding UTI treatment, which depends on the patient and type of urinary tract infection. UTI treatment algorithms are further divided into: 

  • Uncomplicated UTIs 
  • Complicated UTIs 
  • Prophylactic treatment for recurrent UTIs [6] 

What constitutes uncomplicated UTIs are patients who have urinary symptoms, but do not have signs of systemic infections, like fever, flank pain, costovertebral angle (CVA) tenderness, etc. Patients can be male or female, unlike previous guidelines that categorized all males as complicated UTIs. Also, patients with uncomplicated UTIs usually have no underlying health conditions or risk factors that may affect treatment [6].  

Conversely, complicated UTIs occur when patients have systemic symptoms. Patients who are pregnant, have a history of UTIs, or who are considered elderly also fall under complicated UTIs. Patients with pyelonephritis are automatically considered as having complicated UTIs as well. Patients with recurrent UTIs may be prescribed certain low-dose antibiotics for prevention [6]. 

Regardless of the UTI type, below are some of the common antibiotics prescribed: 

  • Trimethoprim-sulfamethoxazole 
  • Nitrofurantoin 
  • Fluoroquinolones 
    • Ciprofloxacin 
    • Levofloxacin 
  • Beta-lactams 
    • Cephalexin 
    • Amoxicillin-clavulanate 
    • Ceftriaxone 
    • Cefdinir 
  • Piperacillin-tazobactam 
  • Meropenem 
  • Fosfomycin 
  • Pivmecillinam

Quiz Questions

Self Quiz

Ask yourself...

  1. What are some factors that classify an uncomplicated UTI? 
  2. What are some factors that classify a complicated UTI? 
  3. What are the different names and types of antibiotics used to treat UTI? 
Pharmacokinetics 

This section discusses the pharmacokinetics of each antibiotic medication used to treat UTIs.  

Trimethoprim-sulfamethoxazole 

Sulfonamides, also called sulfa drugs, are a class of medications commonly used to treat bacterial infections, including UTIs. A common sulfonamide medication used to treat UTIs is sulfamethoxazole formulated with trimethoprim which is sometimes abbreviated as TMP-SMX, TMP-sulfa, or TMP-SMZ [22]. Trimethoprim-sulfamethoxazole is also approved by the Federal Drug Administration (FDA) to treat chronic bronchitis exacerbations, otitis media in children, and shigellosis. 

This medication is also used for prevention and treatment of traveler’s diarrhea, toxoplasmosis, and Pneumocystis jirovecci and Pneumocystis carinii pneumonia. Some other off-label or non-FDA-approved uses are tuberculosis, malaria, listeria, pertussis, and community-acquired pneumonia [10]. 

Since this a combination medication, TMP-SMX works by two different mechanisms of action. Trimethoprim competes with the enzyme dihydrofolate reductase and subsequently stops the production of tetrahydrofolate from converting to folate.  

Sulfamethoxazole, a CYP2CP inhibitor, competes with p-aminobenzoic acid during dihydrofolate synthesis. These two medications combined work against folate production and block bacterial biosynthesis of nucleic acids and proteins. Both medications are metabolized by the liver [10]. 

TMP-SMX is available via oral and intravenous (IV) forms. Adult TMP-SMX oral dosages are typically 160mg/800mg for the treatment of UTI, respectively, and dosages for children under 40 kilograms are weight-based. This medicaiton is best absorbed orally when taken with at least eight ounces of water. Intravenous TMP-SMX is given to hospitalized patients and dosages will vary. Some common side effects of trimethoprim-sulfamethoxazole include:  

  • Nausea and/or vomiting 
  • Rash and photosensitivity 
  • Dizziness 
  • Fatigue 
  • Loss of appetite and anorexia [10] 

As this medication’s mechanism of action interferes with folate production, folate deficiency is also common. More severe side effects may include Stevens-Johnson syndrome, anemia, and Clostridioides difficile (C. diff) diarrhea. This medication should not be prescribed to patients with a sulfa allergy since it can cause anaphylaxis [10]. 

Before prescribing this medication, healthcare providers should also be aware of the precautions and contraindications. Healthcare providers should be cautious when prescribing this medication to patients with decreased kidney function, as it can lead to toxicity and high potassium levels. Therefore, baseline and frequent monitoring of blood urea nitrogen (BUN), creatinine, and potassium levels are helpful.  

Other contraindications include patients with liver failure, hematological disorders, or who are pregnant. TMP-SMX interferes with several medications, including phenytoin, digoxin, diuretics, and rifampin. Many of these medication interactions increase the risk for potential hyperkalemia, medication toxicity, and QT prolongation [10]. 

Quiz Questions

Self Quiz

Ask yourself...

  1. What is the pharmacokinetics of trimethoprim-sulfamethoxazole? 
  2. What are the common side effects of trimethoprim-sulfamethoxazole? 
  3. What are some contraindications of trimethoprim-sulfamethoxazole? 

Nitrofurantoin  

Nitrofurantoin is another antibiotic commonly prescribed to treat urinary tract infections. This medication has been FDA-approved since 1953 to treat and prevent lower UTIs and is commonly considered a first-line treatment. Currently, nitrofurantoin has no other approved or off-label uses. It comes in two different forms, which are monohydrate and macrocrystalline [16]. 

The mechanism of action for nitrofurantoin is not completely understood. However, it is thought to be absorbed by bacterial flavoproteins in the gastrointestinal tract and then further prevents bacterial enzymes from synthesizing DNA, RNA, and cell wall proteins [16]. 

Nitrofurantoin is only available via the oral route. The dosage is usually 100 mg twice daily for UTI treatment and for UTI prophylaxis is 50mg to 100mg once daily. Common medication side effects include:  

  • Nausea and/or vomiting 
  • Diarrhea 
  • Loss of appetite [16] 

Severe reactions, although rare, are pulmonary toxicity where patients may present with fever, chills, cough, and dyspnea. It may also cause liver toxicity, liver failure, and peripheral neuropathy. This medication is contraindicated in patients with a creatinine clearance of less than 60 mL/minute, hemolysis, or who have glucose-6-phosphate dehydrogenase (G6PD) deficiency [16]. 

Healthcare providers should also be aware of considerations when prescribing nitrofurantoin. They must understand that nitrofurantoin should not be prescribed to patients with suspected or confirmed pyelonephritis, since it is only used to treat lower UTIs.  

Nitrofurantoin should not be prescribed to people who are pregnant, especially between 38 to 42 weeks gestation, and neonates. It is also not recommended to give to patients who are 65 years or older due to increased potential adverse effects. For patients who take nitrofurantoin long-term for prophylactic use, liver function tests should be routinely completed and monitoring of pulmonary function [16].

Quiz Questions

Self Quiz

Ask yourself...

  1. What is the pharmacokinetics of nitrofurantoin? 
  2. What are the common side effects of nitrofurantoin? 
  3. What are some contraindications of nitrofurantoin? 

Fluoroquinolones 

Fluoroquinolones are a class of antibiotics used to treat UTIs and other bacterial conditions. Examples of common fluoroquinolones include ciprofloxacin, moxifloxacin, and levofloxacin. However, ciprofloxacin is more commonly used to treat UTIs than the others and therefore, will be the medication reviewed in this section [19]. 

In addition to urinary tract infections, ciprofloxacin is FDA-approved to treat various health conditions. Some common health conditions treated are gonorrhea, chancroids, joint infections, prostatitis, and some gastrointestinal infections. Ophthalmic forms are used to treat corneal ulcers and conjunctivitis, while otic forms may be used in otitis externa [17]. 

Ciprofloxacin’s mechanism of action is considered bactericidal since it works by inhibiting bacterial DNA replication. It acts against DNA topoisomerase and DNA gyrase to hinder DNA replication. Ciprofloxacin is most effective against gram-negative bacteria, but also some gram-positive bacteria. Due to mutations in the DNA gyrase, ciprofloxacin and other fluoroquinolones have begun to show bacterial resistance over the past several years [17]. 

Ciprofloxacin comes in many forms, including oral, IV, ophthalmic, and otic. For the treatment of UTI, this medication is available via oral and IV forms. Recommended dosages are dependent on the severity of UTI and route. Oral dosages for UTI treatment range from 250mg to 500mg twice daily, while IV dosages can range from 200mg to 400mg twice daily to upwards of 400mg every eight hours. Regardless of the administration route, common side effects are nausea and diarrhea. Some serious adverse effects include: 

  • QT prolongation 
  • Hypoglycemia 
  • Hyperglycemia 
  • Photosensitivity [17] 

Ciprofloxacin has an FDA black box warning of tendinitis and tendon rupture, peripheral neuropathy, and myasthenia gravis exacerbation. Due to the effects this medication has on tendons, Achilles tendon rupture, aortic aneurysm, and aortic dissection are also serious adverse effects. If the healthcare provider suspects any adverse effects, including mild tendonitis, the medication should be discontinued immediately.  

Furthermore, when prescribing ciprofloxacin, there are additional considerations and contraindications. As with all medications, ciprofloxacin should not be prescribed to patients with a known allergy to this medication. 

Ciprofloxacin should not be prescribed along with tizanidine, theophylline, or cyclosporine due to interactions. Antacids can also interfere with the absorption of ciprofloxacin and ciprofloxacin toxicity is more likely in older adults. Healthcare providers should encourage patients with diabetes to closely monitor their blood glucose levels at home since this medication can cause hypo- or hyperglycemia [17].

Quiz Questions

Self Quiz

Ask yourself...

  1. What is the pharmacokinetics of ciprofloxacin? 
  2. What are the common side effects of ciprofloxacin? 
  3. What are some contraindications of ciprofloxacin? 
  4. What is the black box warning of ciprofloxacin? 

Beta-lactams 

Beta-lactams are a class of antibiotics used to treat various bacterial conditions, including UTIs. The three main beta-lactams covered below are those commonly used to treat UTI and include cephalexin, amoxicillin-clavulanate, and ceftriaxone. Other beta-lactams that are approved for UTI treatment are cefpodoxime, cefdinir, and cefadroxil, and work similarly to others in this medication family. 

Cephalexin 

Cephalexin is a beta-lactam antibiotic that is classified as a first-generation cephalosporin. It was initially approved by the FDA in 1970 and is widely used throughout healthcare settings. In addition to acute and chronic UTIs, cephalexin is approved to treat upper and lower respiratory infections, bone infections, and otitis media. It is also used to treat surgical site, skin, and soft tissue infections [8]. 

Cephalexin falls under the beta-lactam class since its structure has a beta-lactam ring. This ring inhibits the synthesis of peptidoglycan which further disrupts the bacterial cell wall. More specifically, the beta-lactam ring binds to the penicillin-binding proteins during peptidoglycan synthesis, causing the disruption of the bacterial cell wall and viability [8]. 

Cephalexin is only available via oral route and can be prescribed in tablet, capsule, and suspension forms. Daily dosages from 1000mg to 4000mg for adults and for children, are weight-based and range from 25mg to 100mg per kilogram per day. Some side effects of cephalexin include: 

  • Abdominal pain 
  • Diarrhea 
  • Nausea and/or vomiting 
  • Rash 
  • Candidiasis [8] 

Other reactions may include increased liver enzymes, C. diff colitis, and hemolytic anemia. Although cross-reactivity with penicillin is somewhat uncommon, healthcare providers should use caution when prescribing this medication to patients who are allergic to penicillin. Furthermore, it should not be prescribed to patients with a cephalosporin allergy. Cephalexin also interacts with metformin, causing decreased clearance of metformin from the body.  

If a patient is taking metformin, they should be advised to closely monitor their blood glucose levels since the risk for hypoglycemia is increased. Healthcare providers should also be cautious when prescribing this medication to patients who are taking probenecid. Cephalexin can also increase prothrombin time, which typically requires monitoring, especially for those undergoing anticoagulant treatment [8].

Quiz Questions

Self Quiz

Ask yourself...

  1. What is the pharmacokinetics of cephalexin? 
  2. What are the common side effects of cephalexin? 
  3. What are some contraindications of cephalexin? 

Amoxicillin-clavulanate 

As its name implies, amoxicillin-clavulanate is a combination medication of amoxicillin and clavulanic acid. In addition to treating UTIs, this medication is FDA-approved to treat rhinosinusitis, acute otitis media, skin infections, and aspiration and community-acquired pneumonia. Other non FDA-approved uses are impetigo, chronic obstructive pulmonary disease exacerbations, diabetic foot infections, and human and animal bites [4]. 

Amoxicillin-clavulanate works via two different mechanisms of action since it is a combination medication. The amoxicillin component is a beta-lactam antibiotic and works via the same mechanism as cephalexin described above. Clavulanic acid is a beta-lactamase inhibitor, which prevents bacteria from destroying beta-lactam antibiotics. Thus, the reason why clavulanic acid is often combined with amoxicillin [4]. 

This medication is only available via oral forms, such as suspensions, chewable, immediate-release, or extended-release tablets. Dosages are dependent on the underlying condition being treated, medication form (i.e. immediate- versus extended-release), and the patient’s age. Regardless of dosage, amoxicillin-clavulanate can lead to common gastrointestinal side effects, such as: 

  • Diarrhea 
  • Nausea 
  • Vomiting 
  • Loose stools [4] 

Vaginal candidiasis is another common side effect of amoxicillin-clavulanate. For patients who are breastfeeding, this medication may cause hypersensitivity reactions in infants since it is excreted in breast milk. Additionally, amoxicillin-clavulanate has several drug interactions with medications, including probenecid, oral anticoagulants, allopurinol, and oral contraceptives. For patients on hemodialysis or with severe renal impairment, usually where their creatinine clearance is less than 30 mL/min, dose adjustments are recommended.  

Healthcare providers should monitor patients’ liver enzymes for possible hepatic impairment, and if hepatic injury occurs, stop the medication immediately and follow treatment recommendations accordingly. Since amoxicillin is a penicillin derivative, it should not be prescribed to individuals with a penicillin allergy [4]. 

Quiz Questions

Self Quiz

Ask yourself...

  1. What is the pharmacokinetics of amoxicillin-clavulanate? 
  2. What are the common side effects of amoxicillin-clavulanate? 
  3. What are some contraindications of amoxicillin-clavulanate? 

Ceftriaxone 

Ceftriaxone is another beta-lactam antibiotic used to treat UTIs and is usually an adjunct medication. It is a third-generation cephalosporin that is also used to treat gonorrhea, pelvic inflammatory disease, meningitis, and certain abdominal, respiratory, and joint infections. Additionally, ceftriaxone treats bacteremia, sepsis, and infective endocarditis. Since ceftriaxone belongs to the beta-lactam class, its mechanism of action is the same as previously described cephalexin [18]. 

Ceftriaxone comes in both intravenous and intramuscular (IM) forms since it is not absorbed through the gastrointestinal tract. For UTI treatment, the dosage for adults is 1 to 2 grams IV or IM every 24 hours. In an outpatient setting, ceftriaxone is often given as a single IM dose to patients with pyelonephritis who are not hospitalized. Again, this medication is used as an adjunct medication, so it is given as a single IM dose, followed by another oral antibiotic for UTI treatment. Dosages for children range from 50mg to 75mg per kilogram per day for both IM and IV forms [18]. Some common side effects of ceftriaxone are: 

  • Diarrhea 
  • Nausea  
  • Vomiting 
  • Dysgeusia (metallic or foul taste in the mouth) 
  • Injection site reaction, especially for IM [18] 

Other adverse effects associated with ceftriaxone are hemolytic anemias, neutropenia, and thrombocytosis. It should also be noted that this medication can cause neurological symptoms, cholelithiasis, jaundice, elevated liver enzymes, and pancreatitis [18]. 

Healthcare providers should also review ceftriaxone’s precautions and contraindications. This medication is cross-reactive with penicillin and can cause a hypersensitivity reaction. Furthermore, it should not be prescribed to patients with a cephalosporin allergy. If ceftriaxone is administered through an IV, it must not be mixed with calcium-containing IV solutions or products. Other possible medication interactions are estradiol, cyclosporine, and bumetanide. For patients with liver or kidney impairment, dosages must be adjusted and should not exceed 2 grams per day [18]. 

Quiz Questions

Self Quiz

Ask yourself...

  1. What is the pharmacokinetics of ceftriaxone? 
  2. What are the common side effects of ceftriaxone? 
  3. What are some contraindications of ceftriaxone? 

Cefdinir 

Cefdinir is another beta-lactam antibiotic used to treat UTIs and is also a third-generation cephalosporin. In addition to UTI treatment, cefdinir is approved for the treatment of pneumonia, bacterial infections involving the skin, and respiratory infections of the ears, throat, and sinuses. As cefdinir is a third-generation cephalosporin, its mechanism of action is the same as previously described ceftriaxone. Thus, it interferes with bacterial cell wall synthesis [13]. 

Cefdinir is only available via oral route by either capsule or liquid suspension. Treatment dosages and duration are dependent on the underlying condition it is being used to treat [13]. For UTI, this medication is usually prescribed at 300mg twice daily for 5 to 7 days. However, this course may be extended for patients with pyelonephritis or complicated UTIs. Some common side effects of this medication include: 

  • Nausea and vomiting 
  • Diarrhea 
  • Vaginal itching 
  • Red-tinged stools [13] 

Other more serious side effects may include rash, hives, facial swelling, and difficulty breathing or swallowing. As with all medications, healthcare providers should be aware of this medication’s precautions and contraindications. Cefdinir should not be prescribed to patients with a cephalosporin allergy or who are taking probenecid. It should also be avoided in patients with gastrointestinal diseases, like colitis, and kidney disease. This medication should be taken at least two hours apart from any aluminum, magnesium, or iron supplement. Additionally, healthcare providers should avoid prescribing the oral suspension form to patients with diabetes, since it contains high amounts of sucrose and can potentially raise blood sugar levels [13].

Quiz Questions

Self Quiz

Ask yourself...

  1. What is the pharmacokinetics of cefdinir? 
  2. What are the common side effects of cefdinir? 
  3. What are some contraindications of cefdinir?
Other Antibiotics Used to Treat UTI 

This section reviews other antibiotics used to treat urinary tract infections. Two common additional antibiotics administered in an inpatient setting include piperacillin-tazobactam and antipseudomonal carbapenems, such as imipenem or meropenem. These are usually reserved for patients with at least one risk factor for multidrug-resistant gram-negative organisms [7]. Drug information about meropenem will be discussed in greater detail below. Other less common antibiotics available in the outpatient are fosfomycin and pivmecillinam. Although these medicatios are used less commonly, it is still important to understand their pharmacokinetics.  

Piperacillin-tazobactam 

As mentioned, piperacillin-tazobactam is used to treat multidrug-resistant gram-negative UTIs in an inpatient setting. In addition to treating UTIs, it is approved for the treatment of skin, gynecological, and certain abdominal infections. This medication is a combination of piperacillin (a penicillin antibiotic) and tazobactam (a beta-lactamase inhibitor). Therefore, its mechanism of action is that of both the penicillin and beta-lactam classes as previously described [15]. 

Piperacillin-tazobactam is available in IV form and the dosage is usually 3.375 grams every six hours [7]. Like many antibiotics, some common side effects include: 

  • Diarrhea 
  • Nausea and/or vomiting 
  • Stomach pain [15] 

This medication can also cause mouth sores, sleeping difficulties, and in more severe cases, itching, difficulty swallowing, and wheezing. Piperacillin-tazobactam should not be prescribed to patients who are taking other penicillin or beta-lactam antibiotics or who have an allergy. It interferes with certain medications including, aminoglycosides, anticoagulants, methotrexate, and vancomycin. Additionally, for patients with diabetes, this medication can cause false results with certain glucose tests [15]. 

Quiz Questions

Self Quiz

Ask yourself...

  1. What is the pharmacokinetics of piperacillin-tazobactam? 
  2. What are common side effects of piperacillin-tazobactam? 
  3. What are some contraindications of piperacillin-tazobactam? 

Meropenem 

An antipseudomonal carbapenem, meropenem, is used to treat inpatient multidrug-resistant gram-negative UTIs. Meropenem is also approved for the treatment of pneumonia, intra-abdominal infections, peritonitis, and meningitis [21]. 

This medication’s mechanism of action is similar to beta-lactams, as it falls under the same family of antibiotics. It binds to penicillin-binding proteins and inhibits bacterial cell wall synthesis by inhibiting peptidoglycan [21]. 

Meropenem is only available in IV form and dosages are dependent on the condition being treated. For UTIs, 1 gram is administered every 8 hours. Gastrointestinal side effects are common for this medication and include symptoms like diarrhea, nausea, vomiting, and constipation. Additional adverse effects may include: 

  • Drowsiness 
  • Headache 
  • Insomnia 
  • Depression [21] 

Seizures are also a potential adverse effect, and therefore, healthcare providers must monitor patients for neurological symptoms. Agranulocytosis, thrombocytopenia, gastrointestinal bleeding, and hemolytic anemia are other conditions which have been reported when taking this medication. For patients with renal impairment, the dosage will need to be adjusted. Meropenem also has many medication interactions, with some major ones including afatinib, atogepant, cariprazine, and colchicine [21]. 

Quiz Questions

Self Quiz

Ask yourself...

  1. What is the pharmacokinetics of meropenem? 
  2. What are the common side effects of meropenem? 
  3. What are some contraindications of meropenem? 

Fosfomycin 

Fosfomycin is an antibiotic that is FDA-approved to treat uncomplicated urinary tract infections and is considered a first-line treatment option. In the United States, fosfomycin is only available in oral, powder which is mixed and dissolved in liquid. Furthermore, although this medication is a first-line UTI treatment option, it is not widely available in the United States [20]. 

This medication’s mechanism of action works by interfering with the formation of peptidoglycan precursor UDP N-acetylmuramic acid, also known as UDP-MurNAc. As it acts one step prior to the beta-lactam antibiotic family, Fosfomycin enters the bacteria through the transporter systems L-alpha-glycerophosphate and hexose-6-phosphate. This medication also reduces the ability of bacteria to adhere to the epithelial cells of the urinary tract [9]. 

To treat UTI, a single dose of 3 grams of fosfomycin is given, which is added to about 3 to 4 ounces of cold water to dissolve the medication. Common side effects may include: 

  • Nausea 
  • Diarrhea 
  • Headache 
  • Back pain [14] 

Other serious side effects are joint pain, rash, facial or oral swelling, and jaundice. Healthcare providers should review this medication’s interactions and contraindications. Fosfomycin interacts with medications like cisapride, metoclopramide, and certain vitamins. Healthcare providers should use caution when prescribing to patients with a history of asthma, liver disease, or who are pregnant or breastfeeding [14]. 

Quiz Questions

Self Quiz

Ask yourself...

  1. What is the mechanism of action for fosfomycin? 
  2. What are some common side effects of fosfomycin? 
  3. What are some contraindications of fosfomycin? 

Pivmecillinam 

Pivmecillinam is another antibiotic used to treat lower urinary tract infections and is part of the UTI treatment algorithm. However, the FDA has not approved this medication for use in the United States [11]. Therefore, most of the specific drug information is not available.  

 

 

Considerations for Prescribers 

This section reviews potential considerations when prescribing antibiotics for UTIs. 

Healthcare providers must consider and review several factors when prescribing antibiotics for UTI treatment. First, the medication’s route, dosage, and treatment duration are usually determined by the setting (inpatient versus outpatient), the type of UTI (e.g. empirical, asymptomatic bacteremia, uncomplicated, complicated, or prophylaxis), and the patient’s underlying medical conditions and risk factors. Furthermore, healthcare providers should strive to follow current treatment guidelines, approved uses, and their organization’s protocols when initiating or adjusting these medications. Healthcare providers must review the patient’s medical history, recent lab values, contraindications, and potential side effects.  

Patient Population 

Certain classes of antibiotics should be avoided in specific individuals or patient populations, and thus, healthcare providers must be aware of these precautions, contraindications, and black box warnings. Ciprofloxacin can lead to medication toxicity and hypoglycemia in older adults and must be avoided in this patient population when able [17]. Additionally, prescribing medications, such as TMP-SMZ and cephalexin, should be cautioned in patients with renal impairment [8, 10]. Prescribing nitrofurantoin, TMP-SMZ, cephalexin, and ceftriaxone should be cautioned in patients with liver failure or elevated liver enzymes. Healthcare providers should routinely monitor the patient’s liver enzymes and function tests [8, 10, 16, 18].  

The patient’s gender at birth plays another large factor in antibiotic selection since treatment for males is considered a complicated UTI and antibiotic duration is extended. Furthermore, in patients who are pregnant or breastfeeding, certain antibiotics should not be prescribed, with some including TMP-SMZ and fluoroquinolones. Alternative treatments for patients who are pregnant are amoxicillin-clavulanate or [6]. For patients with chronic UTIs, initial prophylactic treatment should be started for 3 months and then reevaluated thereafter for prevention. Typical low-dose prophylactic antibiotics are TMP-SMX and nitrofurantoin. However, the healthcare provider should strongly consider medication compliance and potential antibiotic resistance [1].  

Allergies 

Healthcare providers should also review the patient’s allergies and cross-reactivity of certain antibiotics. Trimethoprim-sulfamethoxazole should not be prescribed to individuals with a sulfa allergy. Furthermore, healthcare providers should not prescribe patients with a penicillin allergy amoxicillin-clavulanate and should use caution when prescribing these individuals beta-lactams or cephalosporins due to their potential cross-reactivity, although the percentage is low [8, 10]. 

Medication History 

As discussed, certain antibiotics interact with specific medications. Healthcare providers must review the patient’s medication list prior to prescribing antibiotics. For instance, amoxicillin-clavulanate interacts with allopurinol and lessens the effectiveness of oral contraceptives. Patients on oral contraceptives should be instructed to use backup birth control methods while on the antibiotic [4]. Additionally, while interactions may exist medication timing plays an important role. For example, medications such as ciprofloxacin and TMP-SMZ interact with antacids. However, if the antibiotic is taken two hours before or six hours after the antacid, a potential medication interaction is less likely [17]. Cephalexin is better absorbed on an empty stomach while other antibiotics are recommended to be taken with food [8].  

Bacterial Sensitivity 

Some antibiotics do not treat certain strains of bacteria and thus, healthcare providers must be judicious about initial antibiotic selection and following up with the patient about their urine culture results. For example, bacterial growth on the urine culture might not be sensitive to the initial antibiotic prescribed and may be resistant. Therefore, the antibiotic may need to be changed or dual therapy may be needed.  

Also, patients with recurrent UTIs sometimes develop antibiotic resistance to first-line medications for the treatment of UTI, so an alternative medication should be initially prescribed, and a urine culture sent. If the patient is treated frequently for UTIs, then a referral to urology is warranted for further evaluation [6]. In some patients, asymptomatic bacteremia is found on a routine urinalysis completed during an annual comprehensive exam. Healthcare providers should review the current screening and treatment guidelines on asymptomatic bacteria in adults. For most patients, a urine culture should be sent for further evaluation, and antibiotic administration delayed until the culture has resulted [5]. 

Patient Education 

Patients should be instructed on potential medication side effects and signs of adverse reactions. In an outpatient setting, healthcare providers must instruct patients on worsening symptoms and when to seek immediate or emergent treatment. Oftentimes, urinary tract infections move upstream into the kidneys and cause pyelonephritis or urosepsis [6]. 

Quiz Questions

Self Quiz

Ask yourself...

  1. What factors should healthcare providers consider when prescribing antibiotics? 
  2. Which antibiotic can be prescribed during pregnancy? 
  3. Which steps should be taken for patients with recurrent UTIs? 
  4. What health conditions and lab values are important when selecting UTI antibiotics? 

Upcoming Research 

This section reviews upcoming research and medications for UTI treatment. 

The bacteria strain, E. coli, is typically responsible for urinary tract infections. However, this is not the case for all UTIs, and some patients have developed multiple drug-resistant organisms due to recurrent infections. Therefore, there is much research needed on UTI antibiotic treatment to eradicate these organisms. Recent development of immunomodulatory therapy has been considered as well as medications that inhibit bacterial adhesions to the epithelial cells of the urinary tract. Vaccinations against UTI have also shown recent promise, but further research is still needed [3]. Other non-antibiotic therapies are also being researched, like Lactobacillus-containing products (i.e. probiotics) and cranberry supplements [12].

Quiz Questions

Self Quiz

Ask yourself...

  1. Which bacteria commonly causes urinary tract infections?  
  2. What new research is there about antibiotics for UTI treatment? 
  3. Which types of new products are being researched about UTI treatment? 

Conclusion 

As discussed, antibiotic selection for the treatment of urinary tract infections depends on a variety of factors. Healthcare providers should understand the pharmacokinetics, potential side effects, interactions, and contraindications when selecting an antibiotic. They should also follow current clinical guidelines and their facility’s protocols for a more evidence-based approach. Furthermore, ordering a urine culture or referring a patient to a urologist is warranted for patients with recurrent urinary tract infections.

Quiz Questions

Self Quiz

Ask yourself...

Final Reflection Questions 

  1. What differentiates a lower versus upper UTI? 
  2. What are the different names of beta-lactam antibiotics used to treat UTIs? 
  3. Which antibiotics are commonly prescribed for UTI prophylaxis? 
  4. Which antibiotics are not commonly prescribed or available in the United States? 
  5. Which antibiotics are commonly used to treat multi-drug resistant organisms? 
  6. Which antibiotics can be used in outpatient versus inpatient settings? 
  7. What are the two types of fluoroquinolones used to treat UTIs? 
  8. What are some other antibiotics used to treat UTIs? 

References + Disclaimer

  1. Aggarwal, N., Leslie, S.W., & Lotfollhzadeh, S. (Updated 2024, January 11). Recurrent Urinary Tract Infections. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK557479 
  2. Bono, M.J., Leslie, S.W., & Reygaert, W.C. (Updated 2023, November 13). Uncomplicated Urinary Tract Infections. In StatPearls. StatPearls Publishing. Retrieved from  https://www.ncbi.nlm.nih.gov/books/NBK470195 
  3. Butler, D., Ambite, I., Wan, M. L. Y., Tran, T. H., Wullt, B., & Svanborg, C. (2022). Immunomodulation therapy offers new molecular strategies to treat UTIs. Nature reviews. Urology, 19(7), 419–437. https://doi.org/10.1038/s41585-022-00602-4 
  4. Evans, J., Hanoodi, M., & Wittler, M. (Updated 2023, August 16). Amoxicillin Clavulanate. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK538164/ 
  5. Fekete, T. (Last reviewed 2024, January). Asymptomatic bacteriuria in adults. UpToDate. Retrieved from https://www.uptodate.com/contents/asymptomatic-bacteriuria-in-adults 
  6. Gupta, K. (Last reviewed 2024, January). Acute simple cystitis in adult and adolescent females. UpToDate. Retrieved from https://www.uptodate.com/contents/acute-simple-cystitis-in-adult-and-adolescent-females#H207461713 
  7. Gupta, K. (Last reviewed 2024, January). Acute Complicated Urinary Tract Infection (including pyelonephritis) in Adults and Adolescents. UpToDate. Retrieved from https://www.uptodate.com/contents/acute-complicated-urinary-tract-infection-including-pyelonephritis-in-adults-and-adolescents 
  8. Herman, T.F., & Hashmi, M.F. (Updated 2023, August 17). Cephalexin. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK549780 
  9. Kaye, K. S., Rice, L. B., Dane, A. L., Stus, V., Sagan, O., Fedosiuk, E., Das, A. F., Skarinsky, D., Eckburg, P. B., & Ellis-Grosse, E. J. (2019). Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 69(12), 2045–2056. https://doi.org/10.1093/cid/ciz181 
  10. Kemnic, T.R., & Coleman, M. (Updated 2022, November 28). Trimethoprim Sulfamethoxazole. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK513232/ 
  11. Lodise, T. P., Henriksen, A. S., Hadley, T., & Patel, N. (2021). US-Focused Conceptual Health Care Decision-Analytic Models Examining the Value of Pivmecillinam Relative to Current Standard-of-Care Agents Among Adult Patients With Uncomplicated Urinary Tract Infections due to Enterobacterales. Open forum infectious diseases, 8(10), ofab380. https://doi.org/10.1093/ofid/ofab380 
  12. Loubet, P., Ranfaing, J., Dinh, A., Dunyach-Remy, C., Bernard, L., Bruyère, F., Lavigne, J. P., & Sotto, A. (2020). Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections. Frontiers in microbiology, 11, 1509. https://doi.org/10.3389/fmicb.2020.01509 
  13. MedlinePlus. (2024). Cefdinir. MedlinePlus. Retrieved from https://medlineplus.gov/druginfo/meds/a698001.html 
  14. MedlinePlus. (2024). Fosfomycin. MedlinePlus. Retrieved from https://medlineplus.gov/druginfo/meds/a697008.html 
  15. MedlinePlus. (2024). Piperacillin and Tazobactam Injection. MedlinePlus. Retrieved from https://medlineplus.gov/druginfo/meds/a694003.html 
  16. Squadrito, F.J., & del Portal, D. (Updated 2023, May 29). Nitrofurantoin. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK470526 
  17. Thai, T., Salisbury, B.H., & Zito, P.M. (Updated 2023, August 28). Ciprofloxacin. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK535454/ 
  18. Werth, B.J. (Last revised 2022, September). Cephalosporins. Merck Manual. Retrieved from https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/cephalosporins 
  19. Werth, B.J. (Last revised 2022, September). Fluoroquinolones. Merck Manual. Retrieved from https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/fluoroquinolones 
  20. Werth, B.J. (Last revised 2022, September). Fosfomycin. Merck Manual. Retrieved from https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/fosfomycin 
  21. Werth, B.J. (Last revised 2022, September). Meropenem. Merck Manual. Retrieved from https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/carbapenems 
  22. Werth, B.J. (Last revised 2022, September). Sulfonamides. Merck Manual. Retrieved from https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/sulfonamides 

 

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