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Author: Pamela Downey (MSN, ARNP)

Introduction

The categorization of a urinary tract infection (UTI) as acute complicated directs the management of care. Management of complicated UTIs is based on the extent and severity of the infection. Suspect a UTI in elderly or debilitated patients with nonspecific symptoms, such as falls and alerted function or mental status. Evidence is growing, however, that these are not always reliable predictors. When these symptoms occur with symptoms of systemic infection or pyelonephritis, an evaluation for acute complicated UTI is needed.

Signs & Symptoms

Acute complicated UTI should be suspected in patients with complaints of acute lower urinary tract irritative symptoms, which include (Hooten & Gupta, 2021; Meyrien, 2021):

Dysuria
Fever/chills
Flank pain
New or increased incontinence
Patients who otherwise appear clinically ill
Pelvic or perineal pain (in men)
Suprapubic discomfort/pain
Urinary frequency or urgency

It is important to suspect acute pyelonephritis in patients presenting with fever and flank pain, even in the absence of typical symptoms of cystitis (Hooten & Gupta, 2021; Meyrien, 2021).

It is also important to suspect acute complicated UTI in patients with pyuria and bacteriuria who have nonspecific signs of systemic illness, such as (Hooten & Gupta, 2021; Meyrien, 2021):

Delirium
Lethargy
Patients with nonlocalized fever or sepsis

Diagnosis

Urine for both urinalysis and urine culture should be collected with suspected acute complicated UTI. Urinalysis results inform the diagnosis. Since pyuria (i.e., urine containing white blood cells or pus) is present in almost all patients with UTI, its absence suggests an alternative diagnosis, particularly in patients with nonspecific symptoms. As a result, pyuria is consistent with, but not diagnostic of, UTI and pyuria in the bacteriuric patient do not identify symptomatic infection.

The ideal voided urine sample for UTI evaluation accurately represents the bladder bacterial count with minimal contamination by bacteria colonizing the distal urethra and genital mucosa. Theoretically, this would be a clean-catch, midstream sample of the first micturition of the day. But in fact, there is no clinical evidence that this ideal specimen yields more accurate results.

Acute complicated UTI is diagnosed in the following cases (Hooten & Gupta, 2021; Meyrien, 2021):

If symptoms of cystitis are present including:
- Dysuria
- Urinary urgency
- Urinary frequency
- Symptoms of systemic illness
If flank pain or CVA tenderness is present
If there is pyuria and bacteriuria
If CT findings of low attenuation extending to the renal capsule on contrast enhancement, with or without complications or swelling

Management

A urine culture and susceptibility must be completed for all patients. The efficacy of different regimens for acute complicated UTIs has only been done on a few regimens. The following recommendations are based on antimicrobial agents expected microbial spectrum that achieves adequate urinary tract and systemic levels.

Antimicrobial therapy should empirically be started. Factors that must be considered in terms of which antimicrobials are selected include drug resistance, previous antimicrobial use, and results of recent urine cultures. After a broad-spectrum antimicrobial was started empirically, it should be changed based on culture results to ensure the causative agent can be eliminated effectively. Urology can be consulted for suspected or confirmed anatomic abnormalities.

The choice of initial antimicrobial therapy depends on (Hooten & Gupta, 2021):

Susceptibility of prior urinary isolates
Patient issues including allergy, personal tolerability, and history of prior antimicrobial use
Local community resistance prevalence of Enterobacteriaceae
Antimicrobial issues including toxicity, drug interactions with other medications the patient takes, drug availability, and drug cost

Therapeutic Agents

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):

Table 1: Antimicrobial Groups for Treatment
Aminoglycoside Antibiotics:
Mechanism of Action: Aminoglycosides have concentration-dependent bactericidal activity. They bind to the 30S ribosome, thereby inhibiting bacterial protein synthesis.
Agents: Gentamycin Tobramycin Plazomicin	Indications for usage include: Aerobic, Gram-negative bacteria such as Pseudomonas, Acinetobacter, Enterobacter, and some Mycobacteria
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: Amoxicillin-clavulanate Piperacillin-tazobactam	Indications for usage include: Gram-negative bacteria
Class: Carbapenems
Agents: Imipenem Doripenem Ertapenem Meropenem	Indications for usage include: Haemophilus influenza Anaerobes Most Enterobacteriaceae Methicillin-sensitive staphylococci and streptococci, including S. pneumoniae Most Enterococcus faecalis and many P. aeruginosa strains Carbapenems are active synergistically with aminoglycosides against P. aeruginosa, E. faecium, Stenotrophomonas maltophilia and methicillin-resistant staphylococci
Class: Cephalosporins
Agents: Cefadroxil Cefdinir Cefepine Cefiderocol Cefpodoxime-proxetil Ceftazidime Ceftriaxone	Indications for usage include: Gram-positive bacteria Gram-negative bacteria
Class: Penicillin
Agents: Amoxicillin Pivmecillinam	Indications for usage include: Enterococci: Gram-positive bacteria such as E. faecalis and E. faecium Certain gram-negative bacilli such as non-B-lactamase-producing H. influenza, E. coli, and Proteus mirabilis; Salmonella species; and Shigella species
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: Trimethoprim-Sulfamethoxazole (TMP-SMX)	Indications for usage include: Gram-positive bacteria (including some methicillin-resistant Staphylococcus aureus) A broad spectrum of gram-negative bacteria Protozoans Cystoisospora and Cyclospora species The fungus, Pneumocystis jirovecii
Fluoroquinolone Antibiotics:
Mechanism of Action: Fluoroquinolones are effective against both Gram-negative and Gram-positive bacteria.
Agents: Ciprofloxacin Ciprofloxacin-extended release Levofloxacin Moxifloxacin Norfloxacin Ofloxacin	Indications for usage include: Haemophilus influenzae Moraxella catarrhalis Mycoplasma species Chlamydia species Chlamydophila species Legionella species Enterobacteriaceae Pseudomonas eruginosa Mycobacterium tuberculosis Some atypical mycobacteria Methicillin-sensitive staphylococci
Glycopeptide Antibiotics:
Mechanism of Action: Glycopeptide antibiotics inhibit a late stage in bacterial cell wall peptidoglycan synthesis.
Agents: Vancomycin	Indications for usage include: Most gram-positive cocci and bacilli, including all Staphylococcus aureus and coagulase-negative staphylococcal strains, are resistant to penicillins and cephalosporins Many strains of enterococci (via a bacteriostatic mechanism). However, many strains of enterococci and some strains of S. aureus are vancomycin-resistant Methicillin-resistant S. aureus Methicillin-resistant coagulase-negative staphylococci Certain β-lactam – and multidrug-resistant Streptococcus pneumoniae β-Hemolytic streptococci (when β-lactams cannot be used because of drug allergy or resistance) Corynebacterium group JK Viridans streptococci (when β-lactams cannot be used because of drug allergy or resistance) Enterococci (when β-lactams cannot be used because of drug allergy or resistance)
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: Daptomycin	Indications for usage include: Gram-positive bacteria (broad-spectrum activity) Multidrug-resistant gram-positive bacteria (because cross-resistance with other classes of antibiotics does not occur) Vancomycin-resistant Staphylococcus aureus Vancomycin-resistant enterococci Pneumococci with reduced penicillin sensitivity
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: Linezolid	Indications for usage include: Streptococci Enterococci (Enterococcus faecalis and E. faecium) Staphylococci, including strains resistant to other classes of antibiotics Mycobacteria Anaerobes such as Fusobacterium, Prevotella, Porphyromonas, Bacteroides species, or Peptostreptococci
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: Fosfomycin	Indications for usage include: Enterococci (Enterococcus faecalis and E. coli) Gram-negatives such as Citrobacter and Proteus Activity against extended-spectrum β-lactamase-producing pathogens, notably ESBL-producing E. coli

Hospitalization

Admission is individualized. Indications for Hospitalization for complicated UTI include (Hooten & Gupta, 2021):

Sepsis
Critical illness
Concerns regarding patient adherence to the treatment plan
Inability to maintain oral hydration or take oral medications
Marked debility
Pain
Persistently high fever (e.g., >38.4°C/>101°F)
Suspected urinary tract obstruction

Hospitalized Patients with Critical Illness

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).

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.

Outpatient Treatment

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). For patients prescribed fluoroquinolones, make sure to educate them about the adverse effects of uncommon but serious musculoskeletal and neurologic adverse effects associated with these medications.

In regard to the duration of antimicrobial therapy for patients, it is also individualized. 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):

Fluoroquinolones are given for 5 to 7 days
TMP-SMX is given for 7 to 10 days
Beta-lactams are given for 10 to 14 days

A parenteral regimen can be changed to an oral regimen once symptoms have improved and the patient is stable (Hooten & Gupta, 2021).

Underlying Urinary Tract Abnormalities

Antimicrobials alone may not be successful unless such underlying conditions are corrected. Examples of types of urinary obstruction include (Hooten & Gupta, 2021):

Underlying anatomical urinary tract abnormalities
Underlying functional urinary tract abnormalities like neurogenic bladder
Indwelling bladder catheters
Nephrostomy tubes
Urethral stents

Additional management for these patients may be needed. Examples of additional methods of management or intervention include (Hooten & Gupta, 2021):

Increase frequency of catheterization to improve urinary flow
Exchange or removal of a catheter
Urologic consultation
Gynecologic consultation

Follow-Up

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.

Implicit Bias Statement

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.

References

Drew, R. (2021, November). Aminoglycosides. Up To Date. Visit Source.
Drew, R., & Sakoulas, G. (2021, November). Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults. Up To Date. Visit Source.
Drew, R., & Peel, T. (2021, November). Linezolid and tedizolid (oxazolidinones): An overview. Up To Date. Visit Source.
Hooper, D. (2021, November). Fluoroquinolones. Up To Date. Visit Source.
Hooton, T., & Gupta, K. (2021). Acute complicated urinary tract infection (including pyelonephritis) in adults. Up To Date. Visit Source.
Letourneau, A. (2021a, November) Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects. UpToDate. Visit Source.
Letourneau, A. (2021b, November). Combination beta-lactamase inhibitors, carbapenems, and monobactams. Up To Date. Visit Source.
Letourneau, A. (2021c, November). Cephalosporins. Up To Date. Visit Source.
Meyrien, A. (2021, November). Sampling and evaluation of voided urine in the diagnosis of urinary tract infection in adults. UpToDate. Visit Source.

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