Prophylactic Antibiotics for Hydrocephalus

Recruiting at 2 trial locations

Overseen By Erida C Rivas

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Montefiore Medical Center

Must be taking: Antibiotics

Disqualifiers: Recent surgery, Recent antibiotics, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

84 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the optimal duration for administering antibiotics to patients with hydrocephalus who have an external ventricular drain (EVD), a tube that relieves brain pressure. Researchers aim to determine whether antibiotics should be used for just 24 hours or until the EVD is removed. The trial seeks participants over 18 who have experienced a brain bleed or stroke and require an EVD. Participants should not have had recent brain surgeries or infections. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who were on antibiotics within the week prior to admission.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using antibiotics like Nafcillin or Doxycycline for extended periods is generally safe. Studies have found that these antibiotics can reduce infection risk during certain surgeries. For instance, Nafcillin has been used for short durations without major safety concerns. Although the effects of long-term use are still being studied, these antibiotics are usually well-tolerated in the short term.

However, antibiotics can sometimes cause side effects, such as an upset stomach, diarrhea, or allergic reactions. Long-term use can also lead to bacterial resistance. Ongoing research aims to better understand the safety of prolonged use. Participation in a clinical trial can contribute to finding more answers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the trial for prophylactic antibiotics in hydrocephalus patients because it explores the potential benefits of continuous antibiotic use compared to a shorter, 24-hour course. Unlike the standard care options, which typically involve short-term antibiotic use to prevent infections, this trial is investigating whether long-term use of Nafcillin or Doxycycline until the external ventricular drain (EVD) is removed can provide better infection control. This approach could help in reducing complications associated with infections in patients with hydrocephalus, offering a new strategy that might improve patient outcomes.

What evidence suggests that this trial's treatments could be effective for hydrocephalus?

This trial will compare the effects of continuous antibiotic use until the EVD is removed with antibiotics administered for a total of twenty-four hours. Research has shown that using antibiotics for a longer time can help reduce infections in patients with brain fluid drainage tubes, known as ventricular catheters. Studies have found that antibiotics like Unasyn effectively lower the risk of infection when used for an extended period. However, some patients might still need additional medical procedures, such as shunt revision, which involves surgery to fix or replace the tube. For antibiotics like Nafcillin or Doxycycline, short-term use has been shown to reduce infection risk during shunt surgeries, with no major safety concerns reported. Overall, using antibiotics to prevent infections in people with hydrocephalus, a condition where fluid builds up in the brain, has shown promising results. ^{1 6 7 8 9}

Who Is on the Research Team?

David J Altschul, MD

Principal Investigator

Montefiore Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with subarachnoid hemorrhage, intracerebral hemorrhage, or acute ischemic stroke needing an EVD. It's not for those who had brain procedures within the last month, were on antibiotics recently, have low white blood cell counts, are pregnant or imprisoned.

Inclusion Criteria

If my EVD fails, I will be given antibiotics before it's replaced and stay in my treatment group.

Exclusion Criteria

I have not had any brain surgery in the last 30 days.

Prisoners

Pregnant patients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either 24 hours of prophylactic antibiotics or continuous antibiotics until EVD removal

2 weeks

In-person visits for EVD management

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• long term prophylactic antibiotics
• long term prophylactic antibiotics (Nafcillin or Doxycycline)

Trial Overview The study tests if long-term prophylactic antibiotics (Nafcillin or Doxycycline) are beneficial alongside antibiotic-coated EVDs. Participants will either receive antibiotics for 24 hours or throughout their entire EVD treatment duration.

How Is the Trial Designed?

Group I: continuous antibiotic use until the EVD is removed Experimental Treatment 1 Intervention

continuous antibiotic use until the EVD is removed. Nafcillin 1-2 grams every 6 hours (depending on weight) until the EVD is removed. If penicillin allergic Doxycycline 100mg every 12 hours until the EVD is removed.

Group II: antibiotics for a total of twenty-four hours Active Control 1 Intervention

antibiotics for a total of twenty-four hours Nafcillin 1-2 grams every 6 hours (depending on weight) for a total of 24 hours. If penicillin allergic Doxycycline 100mg every 12 hours for a total of 24 hours.

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

Published Research Related to This Trial

Cerebrospinal fluid (CSF) shunt infections are common complications following neurosurgery for hydrocephalus, typically occurring within the first two months post-surgery, with Staphylococcus epidermidis being the most frequent cause.

The standard treatment involves intravenous antibiotics, removal of the infected shunt, and placement of a new shunt after ensuring the CSF is sterile, with vancomycin being the preferred initial antibiotic, especially for methicillin-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment and prevention of infections of cerebrospinal fluid shunts. Fan-Havard, P., Nahata, MC.[2004]

In a study involving six patients with cerebro-spinal fluid shunt infections, daily intrashunt injections of vancomycin combined with systemic antibiotics led to a 67% cure rate without the need for shunt surgery.

The treatment was effective against common organisms like Staphylococcus epidermidis, but two patients required surgery due to shunt malfunction, highlighting the importance of monitoring for complications during antibiotic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Infection of the valves of CSF shunts. Results of local and general antibiotic treatment in 6 cases]. Roualdes, G., Lartigue, C., Boudigue, MD., et al.[2006]

Nafcillin is recommended over methicillin for prophylactic use in shunt surgeries due to its better penetration into cerebrospinal fluid (CSF), although both antibiotics showed low levels in CSF.

The study suggests that while a preoperative dose of 25 mg/kg of nafcillin may reduce infection risk, higher doses should be considered for patients with significantly dilated ventricles, as nafcillin levels were found to be inversely related to ventricular size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic prophylaxis in ventricular shunt surgery. II. Antibiotic concentrations in cerebrospinal fluid. McCullough, DC., Kane, JG., Harleman, G., et al.[2019]

Prolonged antibiotic prophylaxis in patients with ventricular catheters significantly reduced the incidence of cerebrospinal fluid (CSF) infections (3% vs 11%) and extracranial infections (20% vs 42%) compared to those receiving only perioperative antibiotics, based on a study of 228 patients.

While the extended use of antibiotics was effective in lowering infection rates, it also led to the selection of resistant pathogens like MRSA and Candida, highlighting a potential safety concern with this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CSF antibiotic prophylaxis for neurosurgical patients with ventriculostomy: a randomised study. Poon, WS., Ng, S., Wai, S.[2022]

In a study of 18 neonates with Flavobacterium meningitis, those who received effective antibiotic treatment within 8 days of infection had better outcomes, with normal or mildly dilated ventricles, while those treated later developed progressive hydrocephalus and associated complications.

The combination of intravenous rifampicin, moxalactam, and piperacillin was effective in treating patients with normal or mildly dilated ventricles, highlighting the importance of timely intervention and monitoring through daily ultrasound to prevent severe complications like hydrocephalus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Flavobacterium meningitis in the neonates: experience with 18 consecutive cases. Boo, NY., Lim, VK., Yakin, FM., et al.[2004]

A trial was conducted to assess the efficacy of intraventricular vancomycin as antimicrobial prophylaxis during shunt surgery for hydrocephalus, but it failed to enroll the necessary number of patients (only 158 out of the required 712) to provide statistically valid results.

While the trial did not demonstrate significant toxicity from the vancomycin treatment, it reported fewer infections in the test group (2 infections) compared to the control group (5 infections), indicating a potential benefit, but the small sample size limited the ability to draw definitive conclusions about efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective randomised controlled trial of antimicrobial prophylaxis in hydrocephalus shunt surgery. Bayston, R., Bannister, C., Boston, V., et al.[2019]

The use of short-term prophylactic antibiotics, specifically methicillin, during cerebrospinal fluid (CSF) shunt surgery has been associated with a reduction in case infection rates from 10.9% to 8.9% and operative infections from 8% to 2.6%, based on data from a study spanning 1969 to 1978.

The findings suggest that further improvements in preventing shunt sepsis could be achieved by selecting other semisynthetic penicillins that provide higher concentrations in the CSF, indicating a potential for enhanced efficacy in infection prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic prophylaxis in ventricular shunt surgery. I. Reduction of operative infection rates with methicillin. McCullough, DC., Kane, JG., Presper, JH., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6486049/

Route of antibiotic prophylaxis for prevention of cerebrospinal ... Shunt infections can be treated by the administration of long‐term antibiotics, but in most cases shunt revision is required.

2. withpower.com withpower.com/trial/phase-1-subarachnoid-hemorrhage-5-2021-952bf

Prophylactic Antibiotics for Hydrocephalus Research shows that using antibiotics like Unasyn for a longer period can reduce infections in patients with ventricular catheters, but it may lead to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6548496/

Route of antibiotic prophylaxis for prevention of cerebrospinal ... We found that administration of antibiotics is effective in the prevention of shunt infections (very low quality evidence). As the included studies are few, the ...

4. journals.lww.com journals.lww.com/neurosurgery/abstract/1985/07000/antibiotic_prophylaxis_in_cerebrospinal_fluid.1.aspx

Antibiotic Prophylaxis in Cerebrospinal Fluid Shunting Abstract. The authors report a prospective, randomized 18-month study on the effect of prophylactic antibiotic treatment in 152 hydrocephalic patients in ...

5. cns.org cns.org/guidelines/pediatric-hydrocephalus/6-preoperative-antibiotics-for-shunt-surgery-in-ch

6. Preoperative antibiotics for shunt surgery in children with ... The use of preoperative antibiotic agents can be recommended to prevent shunt infection in patients with hydrocephalus.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8407112/

Antibiotic prophylaxis for surgical introduction of intracranial ... The use of systemic antibiotic prophylaxis and the use of antibiotic‐impregnated catheters were associated with a decrease in shunt infection (OR: 0.52, 95% CI ...

7. liebertpub.com liebertpub.com/doi/10.1089/sur.2021.310?doi=10.1089/sur.2021.310

Antibiotic Prophylaxis and Incidence of Infection with ... Conclusions: Antibiotic prophylaxis was not associated with a decreased incidence of CNS infection in patients with EVD or ICP monitors. Evaluation of ...

8. jaad.org jaad.org/article/S0190-9622(12)02194-9/pdf

Rationale for antibiotic prophylaxis in patients with ... In the setting of dental surgery, prophylactic antibiotics are not recommended in patients with hydrocephalus shunts because the risk of developing infection ...

9. mdpi.com mdpi.com/2079-6382/11/7/856

Surgical Antimicrobial Prophylaxis in Neonates and ... To reduce SSI incidence after shunt surgery, antibiotic prophylaxis has been largely used both in adults and children. Antibiotics were given before, during or ...