# Treatment Duration for Complicated UTI — IDSA 2022

## Core Recommendation

For patients with complicated UTI (including acute pyelonephritis) who are **improving clinically on effective therapy**, the IDSA suggests treating with a **shorter course** of antimicrobials rather than the traditional 10-14 day regimen (Conditional, Moderate to Very Low Certainty of Evidence):

| Antibiotic Class | Recommended Duration | Evidence Certainty |
|---|---|---|
| **Fluoroquinolone** (levofloxacin, ciprofloxacin) | **5-7 days** | Moderate |
| **Non-fluoroquinolone** agents (beta-lactams, TMP-SMX) | **7 days** | Very Low to Low |

### Counting Treatment Duration

- Duration is counted from the **first day of effective antibiotic therapy** (i.e., the first day the patient receives an antibiotic to which the pathogen is susceptible)
- If the initial empiric antibiotic is later found to be ineffective based on culture results, the count restarts from the day effective therapy begins

## Fluoroquinolone Short-Course Evidence

### Key Trial: Levofloxacin 5-Day vs Ciprofloxacin 10-Day

A randomized trial compared **levofloxacin 750 mg IV/PO once daily for 5 days** with **ciprofloxacin 400 mg IV BID / 500 mg PO BID for 10 days** for treatment of complicated UTI and acute pyelonephritis:

- Microbiological eradication rates were comparable between 5-day and 10-day courses
- Clinical success rates were similar
- This trial provided the primary evidence for the 5-7 day fluoroquinolone recommendation

### Practical Fluoroquinolone Duration Guidance

```
Complicated UTI on fluoroquinolone therapy
  |
  +--> Clinical improvement by day 3-5?
        |
        +--> YES --> Complete 5-7 days total
        |           5 days may be sufficient for uncomplicated pyelonephritis
        |           7 days preferred if: bacteremia, slow clinical response, or
        |                                complex anatomy (stones, stents)
        |
        +--> NO --> Reassess at 48-72 hours
                    Review cultures, consider imaging, broaden or change therapy
                    If eventually improving, extend to 7 days (or longer if needed)
```

## Non-Fluoroquinolone Duration

### 7-Day Course for Non-Fluoroquinolone Agents

For patients treated with non-fluoroquinolone agents (including IV cephalosporins with oral step-down to beta-lactam or TMP-SMX), the IDSA suggests **7 days** of total therapy.

- Evidence for short-course oral beta-lactams in cUTI is **more limited** than for fluoroquinolones
- The 7-day recommendation is based primarily on extrapolation from fluoroquinolone data and limited beta-lactam trial data
- **Higher oral beta-lactam doses** may be necessary to compensate for lower tissue penetration compared with fluoroquinolones

### Bacteremia from Urinary Source

For patients with **concurrent Gram-negative bacteremia** from a urinary source:

- Treat for **7 days** total (counted from first day of effective therapy)
- This applies whether using fluoroquinolone or non-fluoroquinolone agents
- IV-to-oral transition is still appropriate once improvement criteria are met
- Even bacteremic patients do not routinely require 10-14 days if improving on effective therapy

## When Longer Treatment May Be Needed

The short-course recommendations may not apply to the following situations, where **10-14 days** (or longer) may be appropriate:

| Situation | Rationale |
|---|---|
| **Renal abscess or perinephric abscess** | Abscess requires prolonged therapy and likely drainage |
| **Prostatic involvement** (suspected bacterial prostatitis) | Poor antibiotic penetration into prostate tissue |
| **Persistent bacteremia** (>72 hours despite effective therapy) | May indicate complicated source or endovascular infection |
| **Immunocompromised patients** | Reduced host immune response; limited trial data in this population |
| **Complete urinary tract obstruction** | Inadequate source control may necessitate longer treatment |
| **Slow clinical response** | Persistent fever, worsening symptoms despite effective therapy |
| **Indwelling urinary devices** | Most trials excluded patients with indwelling catheters |

## Treatment Duration Decision Algorithm

```
Patient with complicated UTI on effective antibiotic therapy
  |
  +--> Is the patient clinically improving?
        |
        +--> YES
        |     |
        |     +--> Any complicating factors?
        |           (Abscess, prostatitis, immunocompromised, obstruction, slow response)
        |           |
        |           +--> NO
        |           |     |
        |           |     +--> On fluoroquinolone?
        |           |     |     YES --> Total duration: 5-7 days
        |           |     |     NO --> Total duration: 7 days
        |           |     |
        |           |     +--> Concurrent bacteremia?
        |           |           YES --> Treat for 7 days minimum
        |           |           NO --> Standard short course
        |           |
        |           +--> YES --> Individualize duration (typically 10-14 days)
        |                        Consider infectious disease consultation
        |
        +--> NO (at 48-72 hours)
              |
              +--> Reassess:
                    1. Verify susceptibility on culture results
                    2. Consider imaging (CT abdomen/pelvis) for abscess, obstruction
                    3. Broaden or change antibiotic therapy
                    4. Rule out alternative diagnoses
                    5. Reassess after interventions; restart duration count if therapy changed
```

## De-escalation and Stewardship Principles

- **De-escalate** to the narrowest-spectrum effective antibiotic once culture and susceptibility data are available
- Avoid prolonging broad-spectrum empiric therapy beyond culture results (typically 48-72 hours)
- Fluoroquinolones should be avoided if the patient has been exposed to a fluoroquinolone in the past 12 months due to increased resistance risk
- Widespread fluoroquinolone use has contributed to increasing bacterial resistance and serious adverse effects (tendinopathy, aortic aneurysm, QT prolongation, C. difficile); stewardship programs appropriately focus on reducing fluoroquinolone use

## Limitations

- The primary evidence for 5-day fluoroquinolone therapy comes from a single randomized trial and was conducted during a period of lower fluoroquinolone resistance.
- Evidence for short-course non-fluoroquinolone therapy is limited and largely extrapolated.
- Optimal duration for specific clinical scenarios (e.g., catheter-associated UTI, immunocompromised patients, polymicrobial infections) remains poorly defined.
- The guideline does not address duration for complicated UTI caused by multidrug-resistant organisms specifically; the IDSA AMR guidance document should be consulted for those situations.
