From the Guidelines
For a urinary tract infection (UTI) caused by Pseudomonas and Enterococcus species, imipenem-cilastatin is typically dosed at 500 mg intravenously every 6 hours or 1 gram every 8 hours for 7-14 days, depending on infection severity, as recommended by the most recent guidelines 1.
Key Considerations
- Imipenem is effective against both Pseudomonas and Enterococcus species due to its broad-spectrum carbapenem activity that inhibits cell wall synthesis.
- However, some Pseudomonas and Enterococcus strains may have developed resistance, so susceptibility testing is essential 1.
- For Enterococcus faecalis specifically, imipenem should be combined with ampicillin or vancomycin for synergistic effect.
- Renal dose adjustments are necessary for patients with impaired kidney function:
- For creatinine clearance 41-70 mL/min, reduce to 500 mg every 8 hours.
- For 21-40 mL/min, give 500 mg every 12 hours.
- For ≤20 mL/min, administer 250-500 mg every 12 hours.
Monitoring and Side Effects
- Monitor for seizures (especially with higher doses or in patients with CNS disorders), gastrointestinal side effects, and allergic reactions during treatment.
- The treatment duration should be individualized according to infection sites, source control, the underlying comorbidities, and the initial response to therapy, with a suggested treatment duration of 5-14 days 1.
From the FDA Drug Label
Table 1: Dosage of Imipenem and Cilastatin for Injection (I.V.) in Adult Patients with Creatinine Clearance Greater than or Equal to 90 mL/min Suspected or Proven Pathogen Susceptibility Dosage of Imipenem and Cilastatin for Injection (I.V.) If the infection is suspected or proven to be due to a susceptible bacterial species 500 mg every 6 hours OR 1,000 mg every 8 hours If the infection is suspected or proven to be due to bacterial species with intermediate susceptibility 1,000 mg every 6 hours
The recommended dosing for Pseudomonas and Enterococcus species UTI is as follows:
- For susceptible strains: 500 mg every 6 hours or 1,000 mg every 8 hours.
- For strains with intermediate susceptibility: 1,000 mg every 6 hours. Note that the dosage may need to be adjusted based on renal function, as outlined in Table 3 of the drug label 2.
From the Research
Imipenem Dosing for Pseudomonas and Enterococcus Species UTI
- Imipenem/cilastatin has been used to treat urinary tract infections (UTIs) caused by Pseudomonas aeruginosa and other Gram-negative bacteria 3.
- A study published in 1985 found that 500 mg of imipenem/cilastatin administered intravenously every eight hours was effective in treating complicated UTIs, including those caused by Pseudomonas aeruginosa 3.
- However, there is limited information available on the use of imipenem for treating UTIs caused by Enterococcus species.
- Other antibiotics, such as cefiderocol, have been shown to be effective against Pseudomonas aeruginosa and other Gram-negative bacteria, but may not be effective against Enterococcus species 4.
- Treatment options for UTIs caused by multidrug-resistant (MDR) Pseudomonas spp. include fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, and fosfomycin 5.
- Sulopenem, a new penem antibiotic, has been shown to be effective against MDR Enterobacterales, including ESBL-producing E. coli and Klebsiella pneumoniae, but its efficacy against Enterococcus species is not well established 6.
Dosage and Administration
- The dosage of imipenem/cilastatin for UTIs is typically 500 mg administered intravenously every eight hours 3.
- The dosage of cefiderocol for UTIs is not specified in the available studies, but it is typically administered intravenously every eight hours 4.
- The dosage of sulopenem for UTIs is typically 1000 mg administered intravenously every eight hours, followed by oral stepdown therapy with sulopenem etzadroxil/probenecid 6.
Efficacy and Safety
- Imipenem/cilastatin has been shown to be effective in treating complicated UTIs, including those caused by Pseudomonas aeruginosa, with a high rate of microbiologic eradication 3.
- Cefiderocol has been shown to be effective against MDR Gram-negative bacteria, including Pseudomonas aeruginosa, but its efficacy against Enterococcus species is not well established 4.
- Sulopenem has been shown to be effective against MDR Enterobacterales, including ESBL-producing E. coli and Klebsiella pneumoniae, but its efficacy against Enterococcus species is not well established 6.
- The safety and tolerability of imipenem/cilastatin, cefiderocol, and sulopenem have been reported in various studies, with few serious drug-related adverse events reported 3, 4, 6.