Keywords antibiotic prophylaxis - meningitis - wound infection
Introduction
Postoperative infections are the cause of great morbidity and mortality in a neurosurgical
unit, especially in a developing country such as India. Many risk factors for infection
have been previously described, which include altered sensorium, preexisting infection,
poor nutritional status, emergency surgery, multiple operations, duration of surgery
for more than 4 to 6 hours, entering a sinus, use of implants, urinary catheterization,
cerebrospinal fluid (CSF) leak, external ventricular drainage, and ventilator support.[1 ]
[2 ]
[3 ]
[4 ]
[5 ]
The benefit of perioperative antibiotic prophylaxis on decreasing neurosurgical site
infection/meningitis is well known.[6 ]
[7 ]
[8 ] However, few studies report the data on extraneurosurgical site nosocomial infections,[4 ]
[9 ]
[10 ] and many are limited to an intensive care unit (ICU) setting including several studies
from our own institute.[1 ]
[2 ] Various antibiotic prophylaxis regimens have evolved and been in use over the years.
This study's aim was to assess the current load of postoperative infections in a dedicated
neurosurgical unit and whether they were significantly decreased by appropriate risk-stratified
perioperative variable-duration antibiotic prophylaxis.
Material and Methods
This retrospective analysis was conducted at our institute from January 1, 2007 through
December 31, 2016. All patients undergoing routine, emergency, or redo neurosurgical
procedures at our center during the study period who developed a postoperative culture-proven
infection within 1 month of surgery as identified by the hospital infection control
records were included in the study.
In the postoperative period when patients showed clinical/radiologic signs of infection,
for example, fever greater than 100.4°F, wound site inflammation, CSF leak, neck rigidity,
dysuria, cough with expectoration, leukocytosis more than 11,000, and infiltrates
on chest X-rays, appropriate bodily fluids were sent for culture. Bacterial organism(s)
grown on culture from CSF, blood, endotracheal aspirate, urine, and wound swab/pus
was taken as an objective marker of postoperative infection. A dedicated staff nurse
designated as the infection control nurse visited the Department of Microbiology on
a daily basis and recorded all positive cultures from patients in dedicated neurosurgical
wards and ICUs. These were then compared (name and registration numbers) with the
previous month's operation lists so as to exclude patients who were admitted for prolonged
conservative management. Every month a team of consultants from the Departments of
Neurosurgery and Microbiology reviewed the compiled statistics.
Infections were classified as CSF, blood, pulmonary, urinary, and wound. The total
number of hospital acquired infections and the number of infected patients were recorded
along with the type of different microorganisms in the grown cultures. The year 2007
was chosen as the starting point for this study as before that time neurotrauma was
also catered to at the main institute and it was in 2007 when it was shifted to a
separate dedicated trauma center, away from the main hospital. Therefore, this study
does not include trauma patients who are at a higher risk of developing infections
in the postoperative period.
From 2007 onward through 2013, the neurosurgical patients at our institute were categorized
in three groups and the antibiotics used for prophylaxis were cloxacillin and amikacin.
Class 1:
Uncomplicated surgery of less than 4-hour duration—24 hours of intravenously administered
cloxacillin and amikacin.
Class 2:
Surgery lasting 4 to 6 hours or in whom a breach in sterility was suspected—48 hours
of intravenously administered cloxacillin and amikacin.
Class 3:
Procedures lasting longer than 6 hours, breach of paranasal sinuses, redo or emergency
operations or implants, or immunocompromising conditions such as diabetes mellitus—48
hours of intravenously administered cloxacillin and amikacin followed by cefuroxime
500 mg administered orally every 12 hours and amikacin 500 mg administered intramuscularly/intravenously
every 12 hours for 3 days.
In 2014, the policy was modified with categorization of neurosurgical cases into four
classes and the change of cloxacillin to cefazolin based on input from culture-sensitivity
reports from the Department of Microbiology. The newer classes were as follows:
Class 1:
Clean cases (< 6 hours)—injectable cefazolin and amikacin at induction with postoperative
cefazolin and amikacin for 24 hours.
Class 2:
Clean-contaminated cases (> 6 hours or breach in sterility, e.g., ventriculoperitoneal
[VP] shunt, Ommaya, spinal implants, deep brain stimulation [DBS] implants, electrocorticography
[ECoG] implants, transsphenoidal surgeries, cases in which frontal or mastoid air
cells have been opened)—injectable cefazolin and amikacin at induction with postoperative
cefazolin and amikacin for 48 hours followed by oral cefuroxime for 3 days.
Class 3:
Contaminated cases (emergency cases except penetrating head injury, external ventricular
drains, redo surgeries, osteomyelitis)—injectable cefazolin, amikacin, and Metrogyl
at induction with postoperative cefazolin, amikacin, and Metrogyl for 48 hours followed
by cefazolin and amikacin for 3 days.
Class 4:
Dirty cases (penetrating head injury, abscesses, suspected meningitis)—Cefoperazone-sulbactam,
amikacin, and Metrogyl at induction followed by cefoperazone-sulbactam, amikacin,
and Metrogyl for 7 days with review of culture reports.
We combined the data from 2007 through 2013 and compared them to the infection rates
prevailing over 2014 through 2016.
Over the entire study period from 2007 through 2016, the operating theaters, dedicated
neurosurgical ICUs and wards, and a number of beds have remained the same and neurosurgical
residents rotated equally between two neurosurgical units on a 6 monthly basis. The
types of surgeries, basic preoperative preparations, draping, surgical techniques,
sterilization, and fumigation protocols, etc. were similar over the study period.
Intraoperative normothermia was maintained, and for surgeries lasting more than 6
hours, a single dose of prophylactic antibiotic was repeated.
The institute ethics committee reviewed and permitted this study. Individual patient
consent was not sought as this was a retrospective data audit from the hospital records.
Data were collected from hand-written and later electronic records and entered by
the principal investigator in Microsoft Excel 2016 (Microsoft Corp.). Statistical
analysis was performed using IBM SPSS Statistics Version 23 (IBM Inc.). Continuous
variables were compared with Student's unpaired t -test. A p < 0.05 was considered significant.
Results
Between 2007 and 2016, our department performed nearly 3,000 surgical procedures per
year with nearly a quarter of them being emergency procedures ([Fig. 1 ]). In this 10-year period, out of a total of 30,251 neurosurgical procedures, 2,193
patients had 2,782 culture-proven hospital-acquired infections (HAIs) in the postoperative
period with increasing number of surgical procedures and decreasing infections over
the years ([Fig. 2 ]).
Fig. 1 Stacked bar chart depicting the proportion of routine versus emergency surgical procedures.
Fig. 2 Line chart depicting the increase in number of procedures over the years compared
with the decrease in hospital-acquired infections (HAIs).
The percentage of postoperative infections varied form 12.12% in 2007 to 4.46% in
2016 with a mean rate of 9.45% over 10 years ([Fig. 3 ]). This included meningitis, surgical site, and extraneurosurgical site infections.
The percentage of patients who had culture-proven meningitis after a neurosurgical
procedure came down from 1.58% in 2007 to 0.48% in 2016 with a mean of 0.96% over
10 years ([Fig. 3 ]). The percentage of extraneurosurgical site infections also decreased over the years.
While in 2007 we saw 2.1% bloodstream infections, 2.92% pulmonary infections, 2.95%
urinary tract infections (UTIs), and 2.57% wound infections, they had dropped to 0.69%,
1.17%, 2.08%, and 0.03%, respectively, in 2016 ([Table 1 ]).
Fig. 3 Line chart depicting the trend of culture-proven meningitis and overall hospital-acquired
infections (HAIs) among postoperative patients as a percentage of total surgical procedures
every year.
Table 1
Trend of postoperative infections among neurosurgical patients from 2007 to 2016
Year
Procedures
Meningitis
Blooda
Pulmonaryb
Urinec
Woundd
HAIse
a Blood—bloodstream infections.
b Pulmonary—respiratory infections.
c Urine—urinary tract infections.
d Wound—surgical site infections.
e HAIs—hospital-acquired infections.
Note: Percentages are based on proportion of procedures.
2007
2,846
45 (1.58%)
60 (2.11%)
83 (2.92%)
84 (2.95%)
73 (2.57%)
345 (12.12%)
2008
2,690
23 (0.86%)
59 (2.19%)
98 (3.64%)
42 (1.56%)
40 (1.49%)
262 (9.74%)
2009
2,692
44 (1.63%)
116 (4.31%)
150 (5.57%)
53 (1.97%)
43 (1.60%)
406 (15.08%)
2010
2,825
40 (1.42%)
90 (3.19%)
97 (3.43%)
72 (2.55%)
31 (1.10%)
330 (11.68%)
2011
2,837
36 (1.27%)
86 (3.03%)
133 (4.69%)
74 (2.61%)
41 (1.45%)
370 (13.04%)
2012
3,187
36 (1.13%)
46 (1.44%)
125 (3.92%)
103 (3.23%)
27 (0.85%)
337 (10.57%)
2013
3,307
22 (0.67%)
64 (1.94%)
83 (2.51%)
80 (2.42%)
28 (0.85%)
277 (8.38%)
2014
3,324
11 (0.33%)
26 (0.78%)
47 (1.41%)
62 (1.87%)
8 (0.24%)
154 (4.63%)
2015
3,221
8 (0.25%)
26 (0.81%)
58 (1.80%)
58 (1.80%)
3 (0.09%)
153 (4.75%)
2016
3,322
16 (0.48%)
23 (0.69%)
39 (1.17%)
69 (2.08%)
1 (0.03%)
148 (4.46%)
Total
30,251
281 (0.96%)
596 (2.05%)
913 (3.11%)
697 (2.30%)
295 (1.02%)
2,782 (9.45%)
Comparison Between 2007–2013 and 2014–2016
We found that the rates of culture-proven meningitis, bloodstream infections, pulmonary
infections, wound infections, and overall HAIs were significantly lower in 2014 to
2016 as compared with 2007 to 2013 ([Table 2 ]). However, the percentage of UTIs, although decreased, was not significantly different
between the two time periods.
Table 2
Comparison between postoperative infection rates from 2007–2013 to 2014–2016
Years
Procedures
Meningitis
Blood infections
Pulmonary infections
UTIs
Wound infections
HAIs
Abbreviations: HAI, hospital-acquired infection; UTI, urinary tract infection.
a Mean percentages are based on proportion of procedures; SD, standard deviation.
b
p Value as obtained from unpaired t -test, < 0.05 was considered significant.
2007–2013
20,384
246
521
769
508
283
2,327
Mean (%) ± SDa
1.22 ± 0.36
2.60 ± 0.97
3.81 ± 1.04
2.47 ± 0.56
1.41 ± 0.59
11.52 ± 2.2
2014–2016
9,867
35
75
144
189
12
455
Mean (%) ± SDa
0.35 ± 0.11
0.76 ± 0.06
1.46 ± 0.32
1.91 ± 0.14
0.12 ± 0.10
4.61 ± 0.14
p Valueb
0.004
0.002
0.006
0.144
0.007
0.001
Distribution of Microorganisms Grown on Culture
As seen in [Fig. 4 ], the most common organisms grown on culture have been non–lactose-fermenting gram-negative
bacilli (GNB), including Acinetobacter , Pseudomonas (combined 42%), followed by Enterobacteriaceae (incl. Klebsiella 17%, Escherichia coli 12.8%, Enterobacter 8%, Proteus 2%, and others) and Staphylococcus spp. 16% (incl. methicillin-susceptible Staphylococcus aureus [MSSA], methicillin-resistant Staphylococcus aureus [MRSA], and coagulase-negative Staph ).
Fig. 4 Bar chart depicting the distribution of microorganisms grown on culture from clinical
specimens every year. GNB, gram-negative bacilli; GPS, gram-positive cocci.
While from 2007 to 2009, 24% infections were caused by gram-positive cocci (GPC),
this proportion came down to 7.25% in 2014 to 2016. The proportion of MRSA in our
study has decreased from 8.8% in 2007 to 2009 to a low of 0.2% in 2014 to 2016, with
a mean rate of 5.4% over 10 years from 2007 through 2016.
Discussion
Many studies have reviewed the development of postoperative meningitis and wound infections
following neurosurgical procedures with rates ranging from 0.8 to 6%.[1 ]
[3 ]
[5 ]
[8 ]
[11 ] The benefit of antibiotic prophylaxis on decreasing neurosurgical site infection/meningitis
is well known.[7 ]
[8 ]
[10 ] However, few studies report the data on extraneurosurgical site nosocomial infections.[2 ]
[4 ]
[9 ]
[10 ]
In 1964, the Committee on Trauma of the National Academy of Sciences—National Research
Council in the United States[12 ] classified the surgical wounds based on the risk of contamination from endogenous
sources into four types: clean, clean-contaminated, contaminated, and dirty. These
categories have been validated in neurosurgical practice by Narotam et al[13 ] in 1994 in a prospective study that showed a significant difference in the infection
rates ranging from 0.8% in clean cases, 6% in clean cases with foreign materials as
implants, 6.8% in clean-contaminated cases, to 9.7% in the contaminated cases. A stratified
chemoprophylactic regimen has been followed in our institute since 2000 with various
modifications over the years. After identifying the causative microorganism on culture,
the patients were shifted from the empirical prophylactic regimen to specified sensitive
antibiotics as per the culture-sensitivity reports.
In a study involving 2,320 postoperative neurosurgical ICU patients between 1995 and
1996, Suri et al[2 ] identified Acinetobacter as a common pathogen (24.6% of all infected patients) and found that it was related
significantly to the length of stay in the ICU after surgery. Additional risk factors
included ventilation for more than 5 days, ICP monitoring, and prolonged indwelling
urinary catheter.
We also found Acinetobacter to be a common pathogen among postoperative neurosurgical patients in our study as
it was isolated from CSF (26% of meningitis cases), blood (16% of bloodstream infections),
respiratory secretions (48% of pulmonary infections), urine (8% of UTIs), and wound
cultures (10% of surgical site infections). In our study, the most common organisms
causing meningitis were non–lactose-fermenting GNB (47% of meningitis). The proportion
of Staphylococcus spp. in our study was significantly higher in wound infections (52% in surgical site
infections) and was 13% in meningitis, 35% in bloodstream infections, 5% among pulmonary
infections, and 29% of UTIs.
During a 12-year study period from 1994 to 2006 at our institute by Sharma et al,[9 ] out of a total of 31,927 procedures, 3,686 patients developed 5,171 culture-proven
infections (16.2%). The most common were pulmonary (4.4%), blood (3.5%) followed by
urinary (3%), CSF (2.9%), and wound (2.5%). There was a significant decrease in the
infection rate following the introduction of a risk-stratified, variable-duration,
written antibiotic protocol in 2000. The percentage of culture-proven meningitis and
wound infections were significantly lower in this study compared with the data from
2000 to 2006, as is expected from the exclusion of neurotrauma patients in this study
([Table 3 ]). However, despite a decrease in the overall nosocomial infections from 2007 to
2016 as compared with the data from 2000 to 2006, there has been a rise in the UTIs
in this study.
Table 3
Comparison between postoperative infection ratesa from 2000–2006 to 2007–2016
Years
Procedures
Meningitis
Blood infections
Pulmonary infections
UTIs
Wound infections
HAIs
a Reported as % based on proportion of procedures ± standard deviation.
b Data from Sharma et al.[9 ]
c
p Value as obtained from unpaired t -test, < 0.05 was considered significant.
2000–2006b
20,339
2.12 ± 0.41
2.29 ± 0.67
3.20 ± 0.74
1.18 ± 0.52
2.26 ± 0.49
11.04 ± 2.24
2007–2016 (present study)
30,251
0.96 ± 0.51
2.05 ± 1.19
3.10 ± 1.42
2.30 ± 0.53
1.03 ± 0.79
9.45 ± 3.79
p Valuec
0.000
0.633
0.878
0.001
0.002
0.335
Sharma et al[9 ] identified Staphylococcus spp. as the most common pathogen in cases of nosocomial meningitis (27% of cases),
followed by non–lactose-fermenting GNB (Acinetobacter 15%, Pseudomonas 5%) and Klebsiella (18%) in 2006.
In this follow-up study, we showed that over the course of 10 years from 2007 to 2016,
the proportion of Staphylococcus spp. in meningitis decreased from 24% in 2007 to 8% in 2015 to 2016 with a mean of
13% over the 10-year period. This can be seen to concur with the routine use of antistaphylococcal
antibiotics in prophylactic regimens. Also, as can be seen by the low prevalence of
MRSA infections (5.5% over 10 years), empirical use of broad-spectrum antibiotics
would be fallacious.
According to a retrospective study at NIMHANS, Bangalore, over a period of 7 years
from 2001 to 2007 by Srinivas et al,[14 ] out of 18,092 patients undergoing neurosurgical procedures, 2.2% (415) cases developed
meningitis in the postoperative period. The most common organisms were non–lactose-fermenting
GNB, followed by Pseudomonas , Klebsiella , and Staphylococcus spp.
This study at our institute shows lower infection rates with meningitis in 0.96% cases.
However, there was a comparable distribution of pathogens with non–lactose-fermenting
GNB (Acinetobacter , Pseudomonas ) being the most common (47%), followed by Enterobacteriaceae (Klebsiella , E. coli ) (39%) and Staphylococcus spp. (13%).
Moorthy et al[3 ] prospectively collected data from 2003 to 2011 on patients undergoing nontrauma
cranial surgeries (craniotomies, transsphenoidal procedures, and shunts, excluding
preexisting infections) at a tertiary care center with use of 1-day course of intravenous
chloramphenicol or single dose of ceftriaxone as prophylaxis. They considered CSF
culture positivity in suspected cases as evidence of meningitis that is similar to
the criteria used in our study. They showed a postoperative meningitis rate of 0.8%.
with the most common organism grown from CSF cultures being Staphylococcus spp. (13 out of 27 cases or 48%).
Again, this was contrary to our study wherein the common causative agents for meningitis
were GNB—Acinetobacter (27%) and Pseudomonas (22%) and Klebsiella (15%) with Staphylococcus spp. accounting for only 13% of meningitis cases.
We found that the rates of meningitis, surgical site infection, and extraneurosurgical
site infections from 2014 to 2016 were significantly lower than those in 2007 to 2013,
as mentioned previously in the results. The main difference between these two groups
was the substitution of cefazolin for cloxacillin in the antibiotic prophylaxis regimen,
and we hypothesize that the cause of this significant drop in infection rates may
be due to the better clinical spectrum of cefazolin (a first-generation cephalosporin)
when compared with cloxacillin. Cefazolin has better activity against GNB that are
common pathogens in our setting and also methicillin-susceptible Staphylococcus spp. The proportion of MRSA in our study was on an average 5.5% over 10 years from
2007 through 2016.
The proportion of different microorganisms grown from the samples is also helpful
in identifying the proper empirical prophylactic antibiotics. As can be seen from
our data, non–lactose-fermenting GNB were responsible for 47% of meningitis at our
center reinforcing that adequate gram-negative coverage is required for prophylaxis.
Bloodstream cultures showed nearly equal distribution of GPC and GNB, whereas surgical
site infections showed predominance of Staphylococcus spp. (52%) as can be expected. Most pulmonary infections were caused by Acinetobacter and Pseudomonas (combined 66%) that can be seen as due to ventilator-associated pneumonia among postoperative
patients. UTIs were commonly caused by Enterobacteriaceae (69%), with E. coli and Klebsiella being the most common pathogens.
Aminoglycosides are more active against gram-negative than gram-positive organisms.
The associated ototoxicity and nephrotoxicity require close monitoring of therapy,
and their appeal was thought to be limited.[15 ] However, in Indian setting majority of postoperative infections are caused by gram-negative
organisms.[9 ]
[14 ] This was also confirmed by this study with most of the meningitis, bloodstream,
pulmonary, and urinary tract infections being caused by non–lactose-fermenting GNB
and Enterobacteriaceae. This warrants an inclusion of an aminoglycoside in the prophylactic
regimen.
Cefazolin is a first-generation cephalosporin active against gram-positive bacteria,
methicillin-susceptible staphylococci, and nonenterococcal streptococci. Scher[16 ] found that it provides adequate coverage for many clean and clean-contaminated operations.
He also noted correctly that prophylactic antibiotic needs to be repeated in a prolonged
surgery for optimal benefit.
Given the rise in antibiotic resistance, physicians have a societal and ethical responsibility
to use antibiotics in an appropriate manner. We last reviewed our prophylactic antibiotic
policy in 2014 and plan to undertake another revision in 2019 based on the 5-year
antibiogram from 2014 to 2018, to select the antibiotics that are effective against
prevailing pathogens and reduce the burden of postoperative infections.
Conclusion
Based on this study findings, we can conclude that a risk-stratified, variable-duration
chemoprophylactic protocol helps in reducing postoperative meningitis, surgical site,
and extraneurosurgical site infections in neurosurgical patients. Non–lactose-fermenting
GNB and Enterobacteriaceae are important pathogens among postoperative neurosurgical
patients and antibiotic prophylaxis including first-generation cephalosporin, and
an aminoglycoside is effective in such a setting.
