In general, the third-generation cephalosporins used in the

five included studies (cefotaxime, cefoperazone, ceftriaxone, ceftazidime

or ceftizoxime) are considered to be of clinical efficacy,
favorable pharmacokinetics, and low frequency of adverse effects
as well as good coverage of Gram-negative organisms, especially
those with narrow and broad spectrum _-lactamases [27]. These eatures make third-generation cephalosporins the antibiotic of
choice in many clinical settings.
However, third-generation cephalosporins are generally not
recommended for surgical prophylaxis [7,28]. Despite these recommendations,
they have been accepted by the medical community
and are today in use in many countries as the most common drugs
in surgical prophylaxis. In neurosurgery, some studies [1214]
showed favorable results for third-generation cephalosporins
as prophylactic antibiotics. The RCTs included in this analysis
also aimed to test for other advantages of third-generation
cephalosporins such a superior side effect profile compared to conventional
antibiotics.
Third-generation cephalosporins are increasingly considered
for prophylaxis in neurosurgery mainly because of the observed
changes in the spectrum of bacteria causing SSIs in neurosurgical
patients (toward an increasing number of Gram-negative
SSIs) [27,28]. This is also of particular interest since postoperative
meningitis is mostly caused by Gram-negative bacteria [29,30].
Because organ SSIs in neurosurgery are associated with more
serious consequences, third-generation cephalosporin prophylaxis
was tested. Despite the theoretical advantages of third-generation
cephalosporines for antibiotic prophylaxis such as broad bacterial
coverage, efficacy in other clinical settings, favorable
pharmacokinetics and dynamics, and low frequency of adverse
effects, our meta-analysis indicates that on the basis of available
pooled data there is no convincing superiority of third-generation
cephalosporins over conventional regimes regarding the overall
rate of SSIs or organ SSIs after neurosurgical procedures. Third-generation cephalosporins are erroneously regarded as
favorable for their bloodbrain barrier (BBB) permeability. This
feature was also mentioned as one of the main reasons that this
group of antibiotics was studied in the RCTs which were subsequently
included in our analysis (see Table 2). However, in terms
of BBB permeability third-generation cephalosporins are identical
to other cephalosporins, they poorly pass the bloodbrain barrier
if the meninges are not inflamed a feature largely caused by their
low lipophilicity [35]. Nevertheless, the minimum bactericidal concentrations
(MBCs) of the extended spectrum cephalosporins for
common pathogens are generally low; thus, therapeutic drug concentrations
can easily be achieved in the CSF [35]. That is why
third-generation cephalosporins demonstrate encouraging clinical
efficacy in the treatment (not prophylaxis) of a broad range of
intracranial bacterial infections. Meanwhile, we must be aware that the widespread use of thirdgeneration
cephalosporins has been associated with increases
in extended spectrum _-lactamase (ESBL)-mediated resistance
amongst Gram-negative pathogens, antibiotic-associated diarrhea
due to C. difficile, and MRSA and enterococci [38,39]. Therefore,
there is a call to restrict the use of these agents [40]. In order
to reduce the selection pressure guidelines are careful not to
recommend these compounds for perioperative prophylaxis in
neurosurgery.
5. Conclusions