COMPARATIVE STUDY ON PROPHYLACTIC USE OF AMOXICILLIN AND CLAVULANIC ACID IN COMBINATION VS CEFTRIAXONE IN NEUROSURGERY WARD OF A TERTIARY CARE HOSPITAL WITH ASSESSMENT OF RESISTANCE RATE IN NEUROSURGERY TO ANTIMICROBIALS

ABOUT AUTHORS:
Neehar Dixit, Arun Kumar, Prashant mathur, Preeti kothiyal
Department of clinical pharmacy
Division of Pharmaceutics
SGRRITS, Patel Nagar
Dehradun, 248001
Uttarakhand, India
neehar.dixit007@gmail.com

ABSTRACT
Antimicrobial agents are among the most commonly prescribed drugs and account for 20% of the hospital pharmacy budget. The present study was designed to observe and compare the prophylactic use of antibiotics (amoxicillin+clavulanic acid vs ceftriaxone) in neurosurgery ward of a tertiary care hospital with assessment of resistance rate in neurosurgery to antimicrobials. Total no of 250 patients were included in the study, in this study inclusion of 232 patients  were receiving amoxicillin+clavulanic acid or Ceftriaxone for prophylaxis in neurosugery. The following parameters were included- reduction of fever, reduction of exudates, depression or disappearance of pathogenic bacteria, overall clinical improvement, complications and length of hospitalization stay. Test of significance of two real ratios was applied and the value of Z indicated (Z=36) which is highly significant hence two ratios are not equal. It implied that ceftriaxone was better than amoxicillin+clavulanic acid. Present study conclude that the resistance rate of penicillins is higher than ceftriaxone in neurosurgery ward. Data  also shows that ceftriaxone is the better choice of treatment and it reduces the hospitalization stay of patients and lead to less burden on patient.

REFERENCE ID: PHARMATUTOR-ART-2052

INTRODUCTION:
Antimicrobial agents are among the most commonly prescribed drugs and account for 20% of the hospital pharmacy budget⁽¹⁾. Unfortunately, the benefits of antibiotics to individual patients are compromised by the development of bacterial drug resistance^[2]. Resistance is a natural and inevitable result of exposing bacteria to antimicrobials^[3]. Therefore, the study was conducted to see the effect of two antibiotics namely augmentin and ceftriaxone. Augmentin is an antibiotic of the penicillin type. It is effective against different microorganism such as H. influenzae, N. gonorrhea, E. coli, Pneumococci, Streptococci, and certain strains of Staphylococci^[4]. Addition of clavulanic acid to amoxicillin in augmentin enhances the effectiveness of this antibiotic against many other bacteria that are ordinarily resistant to amoxicillin. Amoxicillin/clavulanic acid (INN) or co-amoxiclav (BAN) is a combination antibiotic consisting of amoxicillin trihydrate, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor^[5]. This combination results in an antibiotic with an increased spectrum of action and restored efficacy against amoxicillin-resistant bacteria that produce β-lactamase.Ceftriaxone (INN)is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins^[7], it has broad spectrum activity against Gram-positive and Gram-negative bacteria^[8]. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy^[9].

MATERIAL & METHODS:
A total no 250 patients were included in the study. Different types of organism were studied. Resistant rate by antibiotic susceptibility testing was observed. Observations were made for ten criteria under this study.viz.reduction of fever, reduction of exudates, depression or disappearance of pathogenic bacteria, Overall clinical improvement, complication, rate of infections , rate of shunt removal, length of hospitalization, adverse effect of drugs and sensitivity of different organism were also recorded. Prospectively recorded data included: patient demographics; laboratory data and value of comorbidity conditions, date of hospital admission, date of surgery; preoperative antisepsis and drapes used during surgery; previous hospitalisation within one year.If a nosocomial infection occurred, aetiology, susceptibility pattern of the isolate, antibiotic therapy and outcome were recorded.  Patient above 16 yrs  were selected for the study . Only the first episode of bacterial postoperative infection was included in the analysis of outcomes. Adverse effects, as determined by analysis of both clinical and laboratory data, were assessed for each patient included in the study. The two parameters i.e primarily rate of infections and secondary crude mortality, rate of shunt removal, rate of remote infections (pneumonia and urinary tract infections), length of hospitalisation,  and adverse effects of drugs used for prophylaxis were selected.

Statistical analysis:
Test of significance of two real ratios was applied to see the efficacy of the test and to find out the better drug.

Microbiological analysis:
Antibiotic susceptibility test and resistance rate was analyzed in different patients.

Results:-
As discuss in table no. 1 total 232 patients were randomly allocated for treatments. In each group 116 patients were selected. Augmentin and ceftriaxone was prophylactically administered in respective groups. Following neurosurgeries were selected for the study i.e. SDH (sub dural haemmorage), EDH (epi dural haemmorage), craniotomy ,shunt, bone flap and head injury.

Table no 1 : Showing no. of patients include in the study.

Table no 2.Demographic and clinical characteristics at study inclusion of 232 patients receiving amoxicillin+clavulanic acid or Ceftriaxone for prophylaxis in neurosugery. Test of significance of two real ratios was applied and the value of Z indicated (Z=36) which is highly significant hence two ratios are not equal.

Fig.1 Shows rate of resistance in neurosurgery ward for several antibiotics like 1 Penicillins, 2 Cephalosporins 3 .Quinolones 4.Macrolide 5 .Vancomycin 6.Carbenapems 7. Polymyxinb.

As per observed in the fig. 1 total 250 patients were selected randomly and analyzed  for

AST  including:-
1 Urine
2 Blood
3 Sputum
4 CSF

On the basis of culture report the RR was found in the following manner for the various antibiotics. 95 % RR was for penicillin, followed by 80%  for cephalosporins, 70% for quinolones,75% for macrolides, 20% for vancomycin, carbenapems shows 15% resistance and polymyxin b is 0% resistance. The study clearly shows high rate of  resistance in patients for penicillin that may be due to over use of penicillins in the surgery.

Discussions:
It has been reported in the comperative study that for gram positive and negative organism cephalosporin are the most effective 90% for tested strain from serum as compared to penicillins. Further more, ceftriaxone in combination with azithromycin reduce the treatment by 5 days as compared to augmentin when given in children with acute otitis media^[12]. In randomized, double-blind comparison  it concludes that ampicillin/clavulanic acid and ceftriaxone both are having same potency in the prevention of surgical-site infections after neurosurgery. In present study we found thatthe  ampicillin/clavulanic acid and ceftriaxone are of similar prophylactic effectiveness in clean neurosurgical operations.  Moreover cost effectivenessof ceftriaxone is approximately 3 times greater than that of ampicillin/clavulanic acid. Thus the findings were in line with the contentions of this study, the following study implicates that ceftriaxone is better than augmentin. Another study suggest that in single doses ceftriaxone shows less side effects in comparision of augmentin according to study conducted in Italy by Tonelli F,Mazzei suggest that in single dose ceftriaxone is way beeter than augmentin .Adverse effects can also affect the  Selection of antibiotic so we can easily say that ceftriaxone is better than augmentin. In our research finding multiple dose administration of ceftriaxone is more toxic but less toxic in single dose daily administration, in our study  amoxicillin+clavulanic acid  treated group 28 patients was found to suffered from post surgical infections, where as in ceftriaxone treated group only 18 patients was found suffered from post surgical infections. Hence it clearly shows that post surgical infections in case of ceftriaxone was more effective as compared to amoxicillin +clavulanic acid. Furthermore in hospitalization stay the mean duration of hospitalization stay in amoxicillin+clavulanic acid treated group is more than ceftriaxone treated group, that clearly indicates that ceftriaxone is better than amoxicillin+clavulanic acid^{13].

Conclusion:
On the basis of above resultsand discussions we  can conclude that we should limit the use of penicillins as the resistance rate is high and should prefer ceftriaxone over penicillin that will basically improve the treatment and the complications in neurosurgery ward.

References:
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2. Talbot TR, Kaiser AB et.al(2005.) Postoperative infections and antimicrobialprophylaxis. In: Mandell GL, Bennett JE,Dolin R, editors.Principle and practice of infectious diseases. 6th ed. Edinburgh: Elsevier/Churchill Livingstone;. p. 999993533e3567.
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4. Murray PR, Baron EJ,et.al Manual of clinical microbiology 2003. 8th ed.Washington: ASM Press; 2003. p. 385e404
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9. Muto CA, Jernigan JA, Ostrowsky BE, et al. SHEA guideline for preventing nosocomial transmission of multidrug-resistantstrains of Staphylococcus aureus and enterococcus. InfectionControl Hosp Epidemiol 2003;24:362e386
10. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CD Definition of nosocomial infection1988. Am J Infect Control 1988;16:128e140
11. Zentner J, Gilsbach J, Felder T. Antibiotic prophylaxis in cerebrospinal fluid shunting: a prospective randomized trial in 129 patients. Neurosurg Rev 1995;18:169e172
12. Djindjian M, Fevrier MJ, Otterbein G, Soussy JC. Oxacillin prophylaxis in cerebrospinal fluid shunt procedures: results of a randomized open study in 60 hydrocephalic patients. Surg Neurology.1986;25:178e180.
13. Lorenzetti C, Ramadan A, Mamie C, Favier J, Berney J. Prevention of infections of cerebrospinal fluid shunts for hydrocephalus.Neurochirurgie 1994;40:233e241.

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