Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05398081 |
| Other study ID # |
UI/EC/21/0099 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2021 |
| Est. completion date |
March 5, 2022 |
Study information
| Verified date |
May 2023 |
| Source |
University College Hospital, Ibadan |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
BACKGROUND: Surgical site infection (SSI) is potentially catastrophic in neurosurgical
procedures, causing poor in-hospital outcomes in more than half of those affected and
significantly increased length of hospital stay. The appropriate and timely use of
prophylactic antibiotics is found to reduce the prevalence of SSIs. At present, several
regimen of antimicrobial agents are used in neurosurgical procedures since the choice of
appropriate antibiotic agent is not fully established. Cephalosporins are among the
frequently used antibiotics for prophylaxis in neurosurgical procedures, with studies
comparing first and second generation Cephalosporins to third generation in neurosurgical
prophylaxis, showing no superiority of the latter over the former. Clearly, comparing
Cefuroxime (a second generation Cephalosporin) to Ceftriaxone (a third generation
Cephalosporin) in neurosurgical procedures will provide more knowledge on the efficacy of
Cefuroxime as antibiotics prophylaxis.
OBJECTIVE: The study aimed to determine the comparative efficacy of cefuroxime versus
ceftriaxone in the prevention of surgical site infection after neurosurgical procedures at
the University College Hospital Ibadan, Nigeria.
METHODS: The study will be a randomized controlled trial recruiting 92 participants.
Participants would be patients undergoing neurosurgical procedures; they will be randomized
to treatment arms (those receiving cefuroxime versus ceftriaxone for antibiotic prophylaxis).
All the study articipants will be followed up for 30 days to assess for the development of
surgical site infection.
DATA ANALYSIS: Data will be collated, computed and analyzed using the Statistical Product and
Service Solutions (SPSS) Version 21. Demographics will be presented using summary statistics;
mean +/- standard deviation and figures (e.g pie chart, histogram). Study outcomes will yield
categorical and continuous variables which will be analyzed using chi-squared test and Z-test
and/or T-test for hypothesis testing.
Description:
BACKGROUND Surgical Site Infection (SSI) is the most common health care-associated infection
in hospitalized patients, accounting for 31% of all infections globally.
The prevalence of SSI is determined by the antibiotics prophylaxis, the duration of
postoperative monitoring, the institution and the type of surgical procedures. It ranges
between 1% and 17% in most surgical specialties. In the Sub-Saharan Africa, the prevalence of
SSI following neurosurgical procedures when two different third-generation cephalosporins
were used as antibiotic prophylaxis in the same institution were 6.9% and 15% respectively.
It is indeed catastrophic, causing poor in-hospital outcomes in upwards of half of those
affected and significantly increased their length of hospital stay. SSI following craniotomy
costs an average of ₤9,283 above the initial cost of treatment to manage, in addition to the
prolonged disablement and reduced functioning of the patient.
Appropriate and timely use of prophylactic antibiotics reduced the prevalence of SSIs from
8.8% to 4.6%. At present, several regimen of antimicrobial agents are used in neurosurgical
procedures in the absence of a 'choice' antibiotic agent. The choice, ideal antibiotics
should have an appropriate antimicrobial spectrum and favourable pharmacokinetics.
Cephalosporin is among the frequently used antibiotics for prophylaxis in neurosurgical
procedures due to its wide spectrum of their effectiveness, good tissue penetration, and the
low toxicity of its first and second generation agents. They are bactericidal agents, with a
beta-lactam ring structure that determines their antibacterial activity and a six-member
dihydrothiazine ring which is responsible for their ability to resist inactivation by certain
bacterial enzymes. They have different antibacterial activity based on substitutions at
position 7 of the Cephalosporin nucleus. Following penetration of the bacterial cell surface,
they attach to bacterial penicillin-binding proteins - proteins thay catalyze critical
cell-wall synthesis and division reactions; thus interrupting of bacterial cell-wall
synthesis and division.
The first and second-generation Cephalosporins also have the pharmacological advantage that
in case of postoperative infection the third and other newer generation Cephalosporin can be
given with only a slight chance of developing early resistance.Third generation
Cephalosporins, due to their better coverage of gram-negative bacteria compared to the first
and second generation agents, have somewhat been put forward since some noticeable change in
spectrum toward more gram-negative bacteria has been observed in the microbiological profiles
of some series on SSI. Mainly gram-positive cocci; (especially S.aureus and S.epidermidis)
are associated with SSI in neurosurgery.
The widespread use of the third generation Cephalosporin has been associated with an increase
in Extended Spectrum β-Lactamase(ESBL)- mediated resistance amongst Gram-negative pathogens,
as well as antibiotic-associated diarrhea due to Clostridium-difficile and Methicillin
Resistant Staphylococcus Aureus(MRSA) and Enterococci. Therefore, there is the need to
restrict the use of third generation Cephalosporins for perioperative prophylaxis in
neurosurgery.
There are studies which have compared first and second generation Cephalosporins to third
generation in neurosurgical prophylaxis, showing no any superiority of the latter over the
former. Cefuroxime is a second-generation cephalosporin effective against Staphylococcus
aureus, groups A and B streptococci, and S pneumonia. It has moderate activity against a
limited number of aerobic Gram-negative bacilli: Escherichia coli, Klebsiella pneumoniae and
Proteus mirabilis, while it is inactive against anaerobic bacteria.
STATEMENT OF PROBLEM The enhanced activities of third-generation cephalosporins and other
novel beta-lactam antibiotics, such as Cefotaxime, Ceftriaxone, Ceftazidime, and Imipenem,
are directed against multi-resistant aerobic gram-negative bacilli, which are exceptional
causes of postoperative infection in neurosurgical patients. These drugs are therefore
conceptually inappropriate for prophylaxis, but are the ones most commonly used, if not the
sole agents of, surgical prophylaxis in most neurosurgical procedures in this environment.
Clearly comparing Cefuroxime a second generation Cephalosporin to Ceftriaxone a third
generation Cephalosporin in neurosurgical procedures in this environment will help resolve
the question of whether the more microbiologically-sound use of lower-generation
antimicrobial agent in surgical prophylaxis is safe, and if so, can help spare and preserve
the higher-generation agent for more specific use and also, it will help to improve knowledge
on the efficacy of Cefuroxime as antibiotics prophylaxis in this environment. It is therefore
hypothesized that second-generation cephalosporins like Cefuroxime would be no less effectual
than the currently preferred third-generation agents (Ceftriaxone, Ceftazidime) in operative
neurosurgical prophylaxis.
GENERAL OBJECTIVE:
The aim of this study is to compare the effectiveness of two perioperative prophylactic
antibiotic regimens Cefuroxime (second generation Cephalosporin) and Ceftriaxone (third
generation Cephalosporin) in the prevention of surgical site infection after neurosurgical
procedures in the University College Hospital Ibadan, Nigeria.
SPECIFIC OBJECTIVES:
To determine the incidence of surgical site infection after clean and clean-contaminated
neurosurgical procedures at the University College Hospital, Ibadan To determine the
bacterial spectrum with the use of cefuroxime and ceftriaxone for antibiotic prophylactic
regimen for neurosurgical procedures.
To determine the cost of antibiotic prophylaxis regimens in neurosurgical procedure in each
sub-group
NULL HYPOTHESIS Cefuroxime would be less effectual than the currently preferred
third-generation cephalosporin agents such as Ceftriaxone in neurosurgical prophylaxis.
ALTERNATE HYPOTHESIS Cefuroxime would be no less effectual than the currently preferred third
generation cephalosporin agents such as Ceftriaxone and in neurosurgical prophylaxis.
