Oral Carbapenem for Serious Infections
Tebipenem pivoxil hydrobromide is the only oral carbapenem available for treating complicated urinary tract infections and acute pyelonephritis in adults, dosed at 600 mg every 8 hours for 7-10 days. 1
Available Oral Carbapenem
Tebipenem pivoxil hydrobromide (also known as SPR994 or tebipenem-PI-HBr) is an orally bioavailable prodrug that converts to the active carbapenem tebipenem after absorption. 2, 3 This represents the first oral carbapenem approved for adult use, though it was previously available in Japan for pediatric patients only since 2009. 2
Approved Indications
The drug demonstrated non-inferiority to intravenous ertapenem in a large phase 3 trial (ADAPT-PO) involving 1,372 hospitalized adults, with clinical cure rates of 93.1% for tebipenem versus 93.6% for ertapenem at test-of-cure. 1, 4
Adult Dosing Regimen
Standard dose: 600 mg orally every 8 hours for 7-10 days 1, 4
- Treatment may be extended up to 14 days in patients with bacteremia 1
- The drug achieves comparable efficacy to IV ertapenem 1 g every 24 hours 1
Renal Function Adjustments
While specific dosing adjustments are not detailed in the current evidence, tebipenem is expected to require renal dose adjustment for patients with altered kidney function due to its high renal clearance, similar to other carbapenems. 4 Clinicians should anticipate the need for dose reduction in moderate-to-severe renal impairment, though precise adjustment protocols await formal FDA labeling.
Pediatric Dosing
The evidence provided does not contain specific pediatric dosing recommendations for tebipenem pivoxil hydrobromide in the context of cUTI or pyelonephritis, though the drug was historically approved in Japan for pediatric use. 2 For general pediatric carbapenem dosing (meropenem/imipenem), guidelines recommend weight-based regimens stratified by gestational and postnatal age. 5
Spectrum of Activity
Tebipenem demonstrates activity against multidrug-resistant Gram-negative uropathogens, including: 1, 2, 3
- Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales
- Fluoroquinolone-resistant strains
- Broad coverage of anaerobic, Gram-positive, and Gram-negative pathogens
The drug displays microbiological equivalency to intravenous carbapenems such as meropenem. 3
Safety Profile
The most common adverse events are: 1, 4
- Mild diarrhea
- Headache
- Nausea
Adverse event rates were nearly identical between tebipenem (25.7%) and ertapenem (25.6%). 1 As with all carbapenems, tebipenem has the potential to decrease seizure threshold. 4
Clinical Context and Stewardship
This oral carbapenem addresses a critical gap for patients with ESBL-producing or fluoroquinolone-resistant uropathogens who would otherwise require hospitalization solely for IV carbapenem administration. 2, 4 The drug enables step-down therapy from IV to oral route, potentially reducing hospital length of stay and preventing admissions. 4
However, carbapenems should be reserved for situations where narrower-spectrum agents are unsuitable. 6 Guidelines emphasize that carbapenems should not be used empirically for community-acquired infections unless specific risk factors are present (prior ESBL colonization within 3 months plus severe sepsis/septic shock, or at least two criteria including recent broad-spectrum antibiotic use, prior hospitalization, or nursing facility residence with indwelling devices). 5
Important Caveats
- Overall microbiological response rates were lower than clinical cure rates (59.5% for tebipenem vs 63.5% for ertapenem), primarily due to asymptomatic recurrent bacteriuria rather than treatment failure. 1, 4
- The drug is specifically studied and indicated for cUTI and pyelonephritis—it should not be extrapolated to other infection types such as pneumonia, bloodstream infections from non-urinary sources, or intra-abdominal infections without supporting data. 1
- For carbapenem-resistant Enterobacterales (CRE), newer agents like ceftazidime-avibactam or meropenem-vaborbactam are preferred over traditional carbapenems. 5