The categorization of a urinary tract infection (UTI) as acute complicated directs the management of care. Management is based on the extent and severity of the infection.
Promptly start empiric antimicrobial therapy. Consider factors for drug resistance, including previous antimicrobial use, and results of recent urine cultures. Adjust the antimicrobial based on culture results. Consult urology for suspected or confirmed anatomic abnormalities.
The choice of initial antimicrobial therapy depends on (Hooten & Gupta, 2021):
Do a urine culture and susceptibility for all patients. The efficacy of different regimens for acute complicated UTIs has only been done on a few regimens. The following antimicrobial agents are those that are most commonly to blame for UTIs.
UTIs are caused by both Gram-negative and Gram-positive bacteria, as well as, by certain fungi. The most frequent cause for both uncomplicated and complicated UTIs is uropathogenic Escherichia coli (UPEC) (Flores-Mireles & Walker et al, 2015; Hooten & Gupta, 2021).
The prevalence of particular pathogens depends partially on the host. As examples (Flores-Mireles & Walker et al, 2015; Hooten & Gupta, 2021):
Risk factors for UTIs with resistant organisms include (Flores-Mireles & Walker et al, 2015; Hooten & Gupta, 2021):
Increasing rates of resistance in uropathogens have been reported globally. For examples (Flores-Mireles & Walker et al, 2015; Hooten & Gupta, 2021):
The following recommendations for therapeutic agents of treatment are based on expected microbial spectrum that achieves adequate urinary tract and systemic levels.
When starting empiric antimicrobial therapy, make sure to consider factors for drug resistance, including previous antimicrobial use, and results of recent urine cultures. Once culture results are obtained, then adjust the antimicrobial of treatment.
The following chart includes the various antimicrobial medication groups, their respective mechanism of action, and their specific indication for usage (Hooten & Gupta, 2021; Drew, 2021; Drew & Sakoulas, 2021; Drew & Peel, 2021; Letourneau, 2021a; Letourneau, 2021b; Letourneau, 2021c; Hooper, 2021):
Aminoglycoside Antibiotics: | |
Mechanism of Action: Aminoglycosides have concentration-dependent bactericidal activity. They bind to the 30S ribosome, thereby inhibiting bacterial protein synthesis. | |
Agents:
| Indications for usage include:
|
β-lactam Antibiotics: | |
Mechanism of Action: β-lactam antibiotics are a class of broad-spectrum antibiotics consisting of all antibiotic agents containing a beta-lactam ring in their molecular structures. Most β-lactam antibiotics inhibit cell wall biosynthesis in bacterial organisms. They are the most widely used group of antibiotics. Resistance to B-lactam bacteria is common. To stop this resistance, β-lactam antibiotics are often given with β-lactamase inhibitors such as clavulanic acid. | |
Class: Beta-lactamase inhibitors combinations | |
Agents:
| Indications for usage include:
|
Class: Carbapenems | |
Agents:
| Indications for usage include:
|
Class: Cephalosporins | |
Agents:
| Indications for usage include:
|
Class: Penicillins | |
Agents:
| Indications for usage include:
|
Co-trimoxazole Antibiotics: | |
Mechanism of Action: Trimethoprim and sulfamethoxazole have a synergistic effect when given together. They are given in a one-to-five ratio in their tablet formulations. | |
Agent:
| Indications for usage include:
|
Fluoroquinolone Antibiotics: | |
Mechanism of Action: Fluoroquinolones are effective against both Gram-negative and Gram-positive bacteria. | |
Agents:
| Indications for usage include:
|
Glycopeptide Antibiotics: | |
Mechanism of Action: Glycopeptide antibiotics inhibit a late stage in bacterial cell wall peptidoglycan synthesis. | |
Agents:
| Indications for usage include:
|
Lipopeptide Antibiotic: | |
Mechanism of Action: Daptomycin is a cyclic lipopeptide antibiotic that binds to the bacterial cell membranes, causing rapid membrane depolarization. This depolarization causes rapid concentration-dependent bacterial death. | |
Agent:
| Indications for usage include:
|
Oxazolidinone Antibiotics: | |
Mechanism of Action: Linezolid is a synthetic antibiotic that inhibits bacterial protein synthesis by binding to rRNA. It inhibits the creation of the initiation complex during protein synthesis, reducing the length of the peptide chains, and decreasing the reaction rate of translation elongation. | |
Agent:
| Indications for usage include:
|
Phosphonic Antibiotics: | |
Mechanism of Action: Fosfomycin is bactericidal and inhibits bacterial cell wall biogenesis by inactivating the enzyme UDP-N-acetylglucosamine-3-enolpyruvyltransferase, also known as MurA. | |
Agent:
| Indications for usage include:
|
Admission is individualized. Indications for Hospitalization for complicated UTI include (Hooten & Gupta, 2021):
For patients with critical illness, those who are getting worse on current therapy, or those with a suspected urinary obstruction, admission to the intensive care unit (ICU) is generally indicated.
The empiric antimicrobial regimen selection approach depends on the risk for infection with MDR gram-negative organisms for patients hospitalized with acute complicated UTIs who are not critically ill and do not have a suspected obstruction (Hooten & Gupta, 2021).
In such patients, the following antimicrobial agents are suggested (Hooten & Gupta, 2021):
PLUS
Other therapeutic agents that are active for some ESBL-producing Enterobacteriaceae and MDR P. aeruginosa isolates and that are effective for acute complicated UTIs are (Hooten & Gupta, 2021):
An infectious disease consult is needed if carbapenem resistance is suspected based on prior susceptibility testing results.
The selection of antimicrobial therapy must be individualized. The community prevalence of MDR organisms must be considered. Narrower spectrum regimens may be indicated. Urine culture and susceptibility should be followed to ensure that the regimen is correct. If feasible, narrow-spectrum antibiotics should be used to complete the treatment.
The rationale for broad coverage is the high risk of adverse outcomes if there is an inadequate response to empiric antimicrobial therapy and the increasing prevalence of MDR organisms. There is a high risk of clinical decompensations for patients with a UTI with urinary tract obstruction.
A broad-spectrum antimicrobial regimen should be used for the treatment of patients with acute complicated UTIs who are critically ill but have no risk factors for multi-drug resistance (MDR) (Hooten & Gupta, 2021).
Imaging is needed to evaluate patients with critical illness or obstruction.
The empiric antimicrobial regimen selection approach depends on the risk for infection with MDR gram-negative organisms for patients hospitalized with acute complicated UTI who are not critically ill and do not have a suspected obstruction (Hooten & Gupta, 2021).
For patients with no risk factors for infection with an MDR gram-negative organism, the following antimicrobial agents are favored (Hooten & Gupta, 2021):
Oral or parenteral fluoroquinolones are alternatives if the urinary isolates within the last three months are susceptible, and the community prevalence of E. coli fluoroquinolone resistance is not higher than 10%.
Other choices are based on the particular pathogen (Hooten & Gupta, 2021):
If there is a risk of infection with an MDR gram-negative organism, use the following agents (Hooten & Gupta, 2021):
Change the regimen for particular pathogens. Carbapenem is used for patients who have a recent (e.g., within the prior three months) history of infection with ESBL-producing organisms. Vancomycin (for MRSA) or Daptomycin or Linezolid (for VRE) is added if either of these is suspected (because of prior urinary isolates or gram-positive cocci on a current urine gram stain.
Patients with acute complicated UTIs who can be treated in an outpatient setting include those who are clinically stable and/or have mild to moderate cases of severity (Hooten & Gupta, 2021). In addition, if rehydration and antimicrobials can be used in an outpatient facility or the emergency department and be followed by oral antimicrobials taken after discharge with close follow-up, these patients can also be managed on an outpatient basis.
As briefly discussed above, the empiric outpatient antimicrobial regimen is selected based on the contraindications and risk factors for infection with an MDR organism (ESBL-producing isolates) (Hooten & Gupta, 2021).
A broad spectrum of antimicrobial activity against most uropathogens (including P. aeruginosa) is provided by fluoroquinolones (Hooten & Gupta, 2021). Fluoroquinolones are comparable or superior to other broad-spectrum antimicrobials, including parenteral regimens, but resistance is increasing. The following fluoroquinolone agents are recommended when there is no risk for MDR and no concerns for fluoroquinolones resistance/toxicity (Hooten & Gupta, 2021):
Give one dose of a long-acting parenteral agent before fluoroquinolone if the community prevalence of fluoroquinolone resistance in Escherichia coli is known to be >10%. These would include (Hooten & Gupta, 2021):
Educate patients about the adverse effects of uncommon but serious musculoskeletal and neurologic adverse effects associated with fluoroquinolones. When there are no risk factors for MDR but concerns with fluoroquinolones contraindications or resistance/toxicity, the management approach depends on the severity of the illness. For those with a mild infection, a single dose of a long-acting parenteral agent followed by a non-fluoroquinolone oral agent is advocated (Hooten & Gupta, 2021).
For patients who cannot use a fluoroquinolone, one dose of a long-acting parenteral agent is recommended (Hooten & Gupta, 2021):
Following the one dose of a long-acting parenteral agent, one of the following oral agents is recommended (Hooten & Gupta, 2021):
In outpatients who are systemically ill or at risk for more severe illness, the parenteral agents should be continued until culture and susceptibility testing results can guide the selection of an appropriate agent.
For outpatients with acute complicated UTI and risk factors for infection with an MDR gram-negative organism but no contraindications to fluoroquinolones, the following regimen is recommended (Hooten & Gupta, 2021):
After Ertapenem, recommendations suggest one of the following (Hooten & Gupta, 2021):
If the patient cannot take a fluoroquinolone or has a high risk for fluoroquinolone resistance (fluoroquinolone-resistant isolate or fluoroquinolone use in the prior three months), order Ertapenem 1 g IV or IM once daily until cultures and susceptibility testing return.
Use the following antimicrobial agents for outpatients with acute complicated UTI and risk factors for infection with an MDR gram-negative organism and who have either contraindications or concerns for fluoroquinolone resistance:
Change a parenteral regimen to an oral regimen once symptoms have improved. Appropriate oral agents to treat acute complicated UTIs include (Hooten & Gupta, 2021):
Occasionally, susceptibility results require a parenteral agent to complete the course of treatment. Outpatient administration of parenteral antimicrobials includes a peripherally inserted central catheter, a preexisting central catheter, or IM injection.
The duration of antimicrobial therapy ranges between 5 to 14 days. The duration depends on the rapidity of clinical response and the antimicrobial chosen to complete the course (Hooten & Gupta, 2021). The following are the general durations of treatment for the listed respective drugs (Hooten & Gupta, 2021):
Longer treatment duration is needed in patients with a nidus of infection, such as a non-obstructing stone that cannot be removed. The duration of antimicrobial therapy need not be extended due to bacteremia in the absence of other complicating factors. There is no evidence that bacteremia portends a worse prognosis (Hooten & Gupta, 2021).
Research indicates that fluoroquinolones' five- or seven-day duration is comparable to longer durations. Limited data evaluate the use of other oral agents for acute complicated UTIs (Hooten & Gupta, 2021).
Antimicrobials alone may not be successful unless such underlying conditions are corrected. Examples of types of urinary obstruction include (Hooten & Gupta, 2021):
Additional management for these patients may be needed. Examples of additional methods of management or intervention include (Hooten & Gupta, 2021):
If antimicrobial therapy is effective, symptoms should improve quickly. It is important that these patients are closely followed. It is recommended that contact is made by telephone or face-to-face within 48-72 hours with outpatients who had pyelonephritis.
Additional evaluation is needed if symptoms worsen after starting antimicrobials, symptoms persist after 48 to 72 hours of treatment, or symptoms recur within a few weeks. This evaluation includes abdominal/pelvic imaging for factors that might be compromising clinical response. Urine culture and susceptibility testing should be repeated, and treatment should be tailored to the susceptibility profile (Hooten & Gupta, 2021). Patients who presented with hematuria repeat the urinalysis several weeks after treatment to check for persistent hematuria.
Mrs. Vinge is a 63-year-old, retired, widowed, not sexually active, Caucasian female who comes to Urgent Care with c/o increasing fatigue, lower back pain with fevers to 103.5◦ self-treated with Tylenol 500 mg PO every 12 hours for the past three days.
This morning upon first urination, she reports gross hematuria. Denies frequency, urgency, dysuria, vaginal discharge, or itching. No sexual activity in the past 20 years. LMP 1999. No travel outside of the country since 2006. No urinary procedures during her entire lifetime. She denies having any prior UTIs in her lifetime.
PMH:
NKDA
Current medications:
Febrile: 102.5 PO-last Tylenol 4 hours ago.
Neuro: Alert, oriented, cooperative, follows all commands appropriately. PERRLA.
HEENT: WNL
Lungs: CTA. No rales, rhonchi, or wheezes.
Cardiac: HR 100 regular, regularity. No murmurs nor rubs. BP 130-140/70-84.
Abdominal: Abdomen soft, non-tender, with bowel sound in all quadrants. CVA tenderness bilaterally.
GU: Urine cloudy with gross hematuria.
PVS: No edema.
Urine dipstick: leukocyte esterase positive; Nitrite positive
Midstream urine specimen collected and sent to the lab for urine culture and susceptibility.
Results of urine culture showed Escherichia coli > 105 CFU units/mL.
Urine susceptibility testing: This shows E. Coli is sensitive to fluoroquinolone antibiotics.
The patient is considered low risk for infection with an MDR gram-negative organism.
Since the community prevalence of fluoroquinolone resistance in E. Coli is <10%, Ciprofloxacin 500 mg orally twice daily for 7 days is prescribed.
Follow-up should be scheduled with her Primary Care physician in seven days or sooner should symptoms worsen.
CEUFast, Inc. is committed to furthering diversity, equity, and inclusion (DEI). While reflecting on this course content, CEUFast, Inc. would like you to consider your individual perspective and question your own biases. Remember, implicit bias is a form of bias that impacts our practice as healthcare professionals. Implicit bias occurs when we have automatic prejudices, judgments, and/or a general attitude towards a person or a group of people based on associated stereotypes we have formed over time. These automatic thoughts occur without our conscious knowledge and without our intentional desire to discriminate. The concern with implicit bias is that this can impact our actions and decisions with our workplace leadership, colleagues, and even our patients. While it is our universal goal to treat everyone equally, our implicit biases can influence our interactions, assessments, communication, prioritization, and decision-making concerning patients, which can ultimately adversely impact health outcomes. It is important to keep this in mind in order to intentionally work to self-identify our own risk areas where our implicit biases might influence our behaviors. Together, we can cease perpetuating stereotypes and remind each other to remain mindful to help avoid reacting according to biases that are contrary to our conscious beliefs and values.