Cefuroxime vs Ceftriaxone for SSI Prevention in Neurosurgery

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.