Gentamicin for Catheter-Associated Infections

Overseen By Hahn Soe-Lin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Must not be taking: Aminoglycosides

Disqualifiers: Positive UA, Bladder injury, Hematuria, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 30 days

400 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Gentamicin for catheter-associated infections?

Research shows that Gentamicin is effective against a wide range of severe infections caused by gram-negative bacteria, including Pseudomonas aeruginosa, which are common in catheter-associated infections. In studies, Gentamicin demonstrated high antibacterial activity and was superior to other similar antibiotics in treating infections. ^{1 2 3 4 5}

Is gentamicin generally safe for humans?

Gentamicin can cause serious side effects, including kidney damage (nephrotoxicity) and hearing or balance problems (ototoxicity), which can be permanent. These effects have been observed in both animal and human studies, and the risk of kidney damage is higher with gentamicin compared to some other similar antibiotics. ^{3 4 6 7 8}

How does the drug Gentamicin differ from other treatments for catheter-associated infections?

Gentamicin is unique because it is an aminoglycoside antibiotic that is effective against gram-negative bacteria and works synergistically with other antibiotics against gram-positive bacteria. However, it is important to note that it can cause serious side effects like kidney damage and hearing loss, which can occur even after a single dose. ^{1 3 6 9 10}

What is the purpose of this trial?

Urinary tract infections in catheterized patients is an unacceptable complication and has been termed a 'never event' by the Center for Medicare \& Medicaid Services (CMS); however there is not consensus among clinicians on how to best prevent CAUTIs. We propose a prospective randomized controlled trial to test the efficacy of prophylactic gentamicin bladder irrigation in elimination of CAUTIs.

Research Team

Hahn Soe-Lin, MD

Principal Investigator

St. Joseph's Hospital and Medical Center, Phoenix

Eligibility Criteria

This trial is for adults over 18 who are admitted with trauma, surgical, or neuro-critical care issues and have a temporary urinary catheter. It's not for those with chronic catheters, bladder injuries, recent urine infections, or allergies to gentamicin or similar antibiotics.

Inclusion Criteria

I was admitted for a serious injury, surgery, or brain-related critical condition.

Indwelling foley catheter in place

I am older than 18 years.

Exclusion Criteria

Chronic indwelling urethral or chronic suprapubic foley catheter

I have had a bladder injury due to trauma.

I have visible blood in my urine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either gentamicin or placebo bladder irrigation for patients with an indwelling foley catheter of greater than 3 days duration

30 days

Daily administration (BID)

Follow-up

Participants are monitored for CAUTI occurrence through positive urine culture

30 days

Treatment Details

Interventions

• Gentamicin

Trial Overview The study is testing if rinsing the bladder with Gentamicin can prevent urinary tract infections in patients with catheters. Participants will be randomly chosen to receive either the Gentamicin rinse or no rinse as a control group.

Participant Groups

Group I: Gentamicin Experimental Treatment 1 Intervention

14.4 mg gentamicin dissolved in 30 mL 0f 0.9% saline administered BID

Group II: Placebo Placebo Group 1 Intervention

30 mL of 0.9% saline administered BID

Gentamicin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Gentamicin for:

• Urinary tract infections
• Septicemia
• Meningitis
• Osteomyelitis
• Skin and soft tissue infections

Approved in European Union as Gentamicin for:

• Urinary tract infections
• Septicemia
• Meningitis
• Osteomyelitis
• Skin and soft tissue infections

Approved in Canada as Gentamicin for:

• Urinary tract infections
• Septicemia
• Meningitis
• Osteomyelitis
• Skin and soft tissue infections

Who Is Running the Clinical Trial?

St. Joseph's Hospital and Medical Center, Phoenix

Lead Sponsor

Trials

69

Recruited

17,400+

Findings from Research

Sisomicin, gentamicin, and a new form of kanamycin sulfate demonstrated high therapeutic efficacy in treating severe infections caused by gram-negative bacteria, with favorable outcomes in 81-90% of patients.

The study highlights the importance of using adequate doses of these aminoglycosides to achieve effective treatment results, indicating their potential as reliable options for managing serious infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Present-day aminoglycosides in the treatment of suppurative-septic diseases]. Lobuseva, AN., Pozdniakova, VP., Firson, AA., et al.[2020]

Aminoglycoside antibiotics, such as gentamicin, tobramycin, and amikacin, are effective against a wide range of gram-negative bacteria, including Pseudomonas aeruginosa, making them important options for treating serious infections.

Amikacin is preferred when there is a strong suspicion of gentamicin resistance, as it can achieve higher serum levels, enhancing its efficacy in resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial agents--Part II. The aminoglycosides: streptomycin, kanamycin, gentamicin, tobramycin, amikacin, neomycin. Brewer, NS.[2013]

In a study of 62 patients treated with aminoglycoside antibiotics, gentamicin sulfate was found to cause renal failure in 55.2% of patients, significantly higher than the 15% observed in those treated with tobramycin sulfate.

This suggests that while both antibiotics can lead to kidney damage, gentamicin poses a greater risk for renal failure compared to tobramycin, highlighting the need for careful monitoring of kidney function in patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical nephrotoxicity of tobramycin and gentamicin. A prospective study. Kumin, GD.[2016]

The study found that sisomycin has a higher nephrotoxic effect compared to other antibiotics like gentamicin, kanamycin, and streptomycin when blood concentrations are equal, indicating a need for careful monitoring of sisomycin levels.

At therapeutic levels, the nephrotoxic effects of sisomycin and gentamicin are similar, with safe serum concentrations determined to be 6 micrograms/ml for sisomycin and 8 micrograms/ml for gentamicin, providing a basis for evaluating safety in new aminoglycosides.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic analysis of the nephrotoxic effect of sisomycin]. Firsov, AA., Egorenko, GG., Eĭromdzhants, AA.[2013]

Gentamycin sulfate demonstrated superior antibacterial activity compared to kanamycin against various clinical strains, including Staphylococcus, E. coli, Proteus, and Pseudomonas aeruginosa, in both in vitro studies and in albino mice with experimental infections.

Gentamycin was particularly effective in treating acute and chronic staphylococcal infections and showed a low LD50 and high chemotherapeutic index, indicating a favorable safety profile while rapidly reducing the presence of the infection-causing bacteria in the animals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experimental study of the chemotherapeutic activity of gentamicin sulfate]. Lobuseva, AN., Petrova, MA., Pozdniakova, VP., et al.[2014]

Gentamicin, while effective against certain bacterial infections, poses a significant risk of ototoxicity, which can lead to permanent vestibular dysfunction, as demonstrated in a case where a patient developed severe balance issues after receiving the drug during surgery.

The case highlights the need for caution in prescribing gentamicin, especially for patients with preexisting conditions like Meniere's Disease, and suggests considering alternative antibiotics for those with penicillin allergies to avoid serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Debilitating Gentamicin Ototoxicity: Case Report and Recommendations Against Routine Use in Surgical Prophylaxis. Kalmanson, OA., McLoughlin, KC., Kiser, TH., et al.[2023]

In a study involving 236 patients with suspected Staphylococcus aureus endocarditis, the addition of low-dose gentamicin to standard antibiotic therapy was associated with a higher risk of nephrotoxicity, with 22% of patients experiencing decreased kidney function compared to 8% in those who did not receive gentamicin.

The findings suggest that low-dose gentamicin should not be routinely used in treatment protocols for S. aureus bacteremia and endocarditis due to its potential harm and lack of clear benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Cosgrove, SE., Vigliani, GA., Fowler, VG., et al.[2022]

In a study involving 26 albino guinea pigs, gentamicin administered at doses of 4 mg/kg/day and 2.5 mg/kg every 12 hours for 10 to 14 days did not cause any observable damage to external ciliary cells (ECC) in the cochlea, as assessed by distortion product otoacoustic emissions (DPOAE).

Morphological analysis using scanning electron microscopy (SEM) also showed no lesions or functional alterations in the ECC, suggesting that these dosing regimens may be safe in terms of preserving cochlear function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental morphological and functional study of gentamicin cochleotoxicity using the regular dose given to neonates. Baggio, CL., Silveira, AF., Hyppolito, MA.[2019]

1-N HAPA gentamicin B is a new aminoglycoside antibiotic effective against a wide range of bacteria, including Staphylococcus aureus and various Enterobacteriaceae, showing inhibition in 78% of Pseudomonas aeruginosa isolates at a concentration of 12.5 micrograms/ml.

The antibiotic demonstrated similar efficacy to amikacin against both sensitive and resistant bacterial strains and exhibited synergistic effects when combined with carbenicillin, particularly against Gram-negative bacteria like Pseudomonas and Serratia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1-N HAPA gentamicin B, a new aminoglycoside active against gentamicin resistant isolates--activity compared to other aminoglycosides. Neu, HC., Fu, KP.[2019]

Gentamicin is an effective antibiotic for treating gram-negative infections, but its residue can remain in the kidney cortex of beef steers for months after administration, which is monitored using the FAST test.

In a study with eight steers, despite kidney gentamicin levels ranging from 91 to 193 ng/g after 7 to 10 months, all FAST tests were negative, indicating that the drug was below the acceptable limit for residues at slaughter.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of tissue-fluid correlations to estimate gentamicin residues in kidney tissue of Holstein steers. Chiesa, OA., von Bredow, J., Heller, D., et al.[2006]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Present-day aminoglycosides in the treatment of suppurative-septic diseases]. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Antimicrobial agents--Part II. The aminoglycosides: streptomycin, kanamycin, gentamicin, tobramycin, amikacin, neomycin. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical nephrotoxicity of tobramycin and gentamicin. A prospective study. [2016]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic analysis of the nephrotoxic effect of sisomycin]. [2013]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Experimental study of the chemotherapeutic activity of gentamicin sulfate]. [2014]

6. United States pubmed.ncbi.nlm.nih.gov

Debilitating Gentamicin Ototoxicity: Case Report and Recommendations Against Routine Use in Surgical Prophylaxis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. [2022]

8. Brazil pubmed.ncbi.nlm.nih.gov

Experimental morphological and functional study of gentamicin cochleotoxicity using the regular dose given to neonates. [2019]

9. England pubmed.ncbi.nlm.nih.gov

1-N HAPA gentamicin B, a new aminoglycoside active against gentamicin resistant isolates--activity compared to other aminoglycosides. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Use of tissue-fluid correlations to estimate gentamicin residues in kidney tissue of Holstein steers. [2006]