# IV-to-Oral Antibiotic Transition for Complicated UTI — IDSA 2022

## Recommendation

In patients with complicated UTI (including acute pyelonephritis) treated initially with parenteral therapy who are **clinically improving**, **able to take oral medication**, and for whom an **effective oral option** is available, the IDSA suggests transitioning to oral antibiotics rather than continuing parenteral therapy for the remaining treatment duration (Conditional, Low Certainty of Evidence).

This recommendation applies to patients **with or without** concurrent Gram-negative bacteremia from a urinary source.

## Criteria for IV-to-Oral Switch

All of the following criteria must be met before transitioning from IV to oral antibiotics:

| Criterion | Details |
|---|---|
| **Clinical improvement** | Defervescence (temperature trending toward normal), hemodynamic stability, improving symptoms (reduced flank pain, reduced dysuria) |
| **Oral tolerance** | Patient is able to take and absorb oral medications (functioning GI tract, no persistent vomiting) |
| **Effective oral option available** | An oral antibiotic exists to which the isolated organism is susceptible, or a reasonable empiric oral option can be identified |
| **Source control** | Any obstructing stones, abscesses, or anatomic abnormalities have been addressed or are being managed |

## Timing of Switch

- Transition should occur **as soon as the patient is improving clinically** rather than waiting for a fixed number of IV days
- There is no mandated minimum duration of IV therapy before switching, provided the criteria above are met
- Most patients can be considered for switch within **48-72 hours** of initiating effective IV therapy

## Oral Step-Down Antibiotic Options

### Preferred Oral Agents

| Agent | Oral Dose | Frequency | Notes |
|---|---|---|---|
| **Levofloxacin** | 750 mg | Once daily | Near-complete oral bioavailability (~99%); can be used as direct step-down from IV levofloxacin |
| **Ciprofloxacin** | 500-750 mg | Twice daily | High bioavailability (~70-80%); avoid if fluoroquinolone used in past 12 months |
| **TMP-SMX** | 1 DS tablet (160/800 mg) | Twice daily | Use only if susceptibility confirmed; high urinary concentrations |

### Other Oral Agents (Less Well Studied for cUTI)

| Agent | Oral Dose | Frequency | Notes |
|---|---|---|---|
| **Amoxicillin-clavulanate** | 875/125 mg | Three times daily | Evidence for cUTI is limited; may require higher doses for adequate tissue penetration |
| **Cephalexin** | 1000 mg | Four times daily | First-generation cephalosporin; higher doses may be needed for cUTI vs cystitis |
| **Cefpodoxime** | 200 mg | Twice daily | Third-generation oral cephalosporin; limited cUTI-specific data |

### Important Caveats on Oral Beta-Lactams

- Evidence supporting short-course therapy with oral beta-lactams in cUTI is **more limited** than for fluoroquinolones
- **Higher dosing strategies** may be required to achieve adequate urinary and tissue concentrations compared with uncomplicated cystitis dosing
- When using oral beta-lactams for step-down, a full **7-day** course (rather than 5-day) is recommended

## Clinical Decision Algorithm for IV-to-Oral Switch

```
Patient on IV antibiotics for complicated UTI
  |
  +--> Reassess daily (or at minimum every 48 hours)
        |
        +--> Is the patient clinically improving?
        |     |
        |     +--> NO --> Continue current IV therapy
        |     |           Reassess in 24 hours
        |     |           If no improvement at 48-72 hours:
        |     |             --> Review culture results
        |     |             --> Consider imaging (CT abdomen/pelvis)
        |     |             --> Broaden antibiotic coverage
        |     |             --> Rule out abscess, obstruction, or alternative diagnosis
        |     |
        |     +--> YES --> Can the patient tolerate oral medications?
        |           |
        |           +--> NO --> Continue IV therapy
        |           |           Reassess oral tolerance daily
        |           |
        |           +--> YES --> Is an effective oral option available?
        |                 |
        |                 +--> Check susceptibility data from urine/blood cultures
        |                 |
        |                 +--> Susceptible oral option available?
        |                       |
        |                       +--> YES --> SWITCH TO ORAL THERAPY
        |                       |           Preferred: fluoroquinolone or TMP-SMX
        |                       |           Alternative: oral beta-lactam (higher dose)
        |                       |           Complete remaining days of total therapy orally
        |                       |
        |                       +--> NO --> Continue IV therapy for full course
        |                                   Consider ID consultation
```

## Special Considerations

### Bacteremia with a Urinary Source

- Patients with **Gram-negative bacteremia** from a urinary source **can still be transitioned** to oral antibiotics once improving, provided culture-guided oral options are available
- Total treatment duration for bacteremic cUTI: **7 days** (counted from first day of effective therapy)
- This recommendation applies to Gram-negative bacteremia only; Gram-positive bacteremia (e.g., enterococcal) may require individualized management

### Fluoroquinolone Bioavailability Advantage

- **Levofloxacin** has near-complete oral bioavailability (~99%), making IV-to-oral transition essentially seamless
- **Ciprofloxacin** oral bioavailability is approximately 70-80%
- These high oral bioavailability profiles support the IV-to-oral switch recommendation

### When NOT to Switch to Oral

Consider continuing IV therapy in the following situations:
- Persistent fever or hemodynamic instability
- Inability to tolerate oral medications
- No effective oral options based on susceptibility testing
- Undrained abscess or unresolved obstruction
- Concern for poor oral absorption (e.g., severe ileus, malabsorption)

## Limitations

- The evidence supporting IV-to-oral transition comes primarily from observational studies and limited randomized data (Low Certainty of Evidence).
- Most supporting studies excluded patients with indwelling catheters, septic shock, immunocompromised states, severe renal insufficiency, or functional/structural urinary tract abnormalities.
- Evidence for oral beta-lactam step-down is significantly more limited than for fluoroquinolones or TMP-SMX.
- Optimal timing of the switch (e.g., 24 hours vs 48 hours vs 72 hours) has not been established in randomized trials for this specific population.
