A Study on Clinical Profile of Patients with Acute Severe Pancreatitis on Carbapenem versus Non-Carbapenems

D. Sarojini*, P. Sunitha, L.K. Kanthal, K. Lavanya, Kausik Bhar

Koringa College of Pharmacy, Korangi-533461, Tallarevu (M), East Godavari Dist., Andhra Pradesh.

ABSTRACT:

The present study focussed on the clinical profile of patients with acute severe pancreatitis on carbapenem Vs non carbapenems. Out of 55 patients 22 patients were given carbapenem antibiotics and rest were given non carbapenem antibiotics which comprises of cephalosporins, fluoroquinolones, Piperacillin +tazobactum, Metronidazole. In the carbapenem group 20 patients were initially on cephalosporins and later they were started on carbapenem as they were not improving. In these 20 patients, renal failure is observed in 14 patients and respiratory failure in 6 patients. All these 20patients survived and they stayed in hospital for 3-5weeks.Two patients in carbapenem group died and they had renal and respiratory failure even they were started on carbapenem in the first week. These two patients stayed in hospital for 3weeks. A total of 33 patients were given non carbapenem antibiotics. Out of 33patients 16patients had renal failure and 12patients had multiorgan failure. 8patients had local complications in form of multiple fluid collections and necrosis more than 50%. 22out of patients received cefaperazone+sulbactum with Fluoroquinolones. 7 patients received only Piperacillin+Tazobactum with Fluoroquinolones. 4 patients received only Fluoroquinolones. 30patients who were on cephalosporins stayed 2-3weeks and all 30 patients improved and were discharged. 3 Patients out of 33 died in the first week due to multiorgan failure. This study conclude that cefaperazone sulbactum along with quinolone is a good first choice antibiotic and reserve the imipenem for sicker and non responders to cephalosporins.

KEYWORDS: Acute severe Pancreatitis, Carbapenem antibiotics, Non-Carbapenem, Respiratory failure, Multiorgan failure, Fluoroquinolones.

INTRODUCTION:

Acute pancreatitis is an acute inflammatory process of the pancreas, with variable involvement of other regional tissues or remote organ systems (Atlanta clinical definition)^[1]. Acute pancreatitis acute pancreatic necrosis ^[2] presents with Upper abdominal pain and is associated with vomiting, constipation, decreased urine output, dyspnoea. In general, serum lipase is thought to be more sensitive and specific than serum amylase in the diagnosis of acute pancreatitis.^[3] The clinical abdominal findings range from mild tenderness to rebound and absent bowel sounds. Acute severe pancreatitis is diagnosed by clinical features, 3 times elevation of amylase or lipase, and ultrasound or CT abdomen imaging. While many patients will recover from the attack with only general supportive care, about 1 in 5 will develop severe acute pancreatitis ^[4] and 20% of these patients may succumb to it.^[5] In one large study, there were no patients with pancreatitis who had an elevated amylase with a normal lipase.^[6]The course of pancreatitis may be mild or severe. The severe acute pancreatitis is associated with organ failure ^[7] and/or local complications, such as necrosis,^[8] abscess, or pseudo cyst . Mild acute pancreatitis is associated with minimal organ dysfunction and an uneventful recovery, and lacks the described features of severe acute pancreatitis.^[9] There is no role of antibiotics in acute mild pancreatitis.

Antibiotics are indicated in acute severe pancreatitis. There are many queries regarding starting of antibiotics on demand or prophylactic, choice of antibiotic, duration of antibiotic. biliary pancreatitis usually occurs in older adults. These patients often have a history of cholelithiasis or intermittent, postprandial right upper- quadrant pain^[10]. Meta analyses of antibiotics in acute severe pancreatitis ^[11] had established the role of antibiotics. A commonly used classification system (the Atlanta classification) divided acute pancreatitis in to two broad categories.

1) Mild (oedematous and interstitial) acute pancreatitis 2) Severe (usually synonymous with necrotizing) acute pancreatitis.^[12]

Now most of gastroenterologists opine that the antibiotics should be given on demand when there is persistent fever, leucocytosis and new onset organ failure. The choice of antibiotic is cephalosporin versus carbapenem. Carbapenems have good penetration into pancreatic tissue. The other antibiotics which are used Piperacillin- tazobactum, Fluroquinolones, moxifloxacin, Metronidazole. In one study, organ failure within 72hours of admission was associated with the presence of extended pancreatic necrosis and a mortality rate 42%^[13]. While computed tomography is considered the gold standard in diagnostic imaging for acute pancreatitis,^[14] magnetic resonance imaging (MRI) has become increasingly valuable as a tool for the visualization of the pancreas, particularly of pancreatic fluid collections and necrotized debris.^[15]

Methodology:

The study was carried out in Gastroenterology and Hepatology ward with the consent of Head of the Department, Gastro enterology, Apollo Hospitals, Kakinada (East Godavari Dist., A.P.). All the records of the patients who were admitted with the diagnosis of acute pancreatitis were screened and those patients with severe pancreatitis were included in the study and those with mild pancreatitis and underlying chronic pancreatitis, malignancy were excluded. The patient’s demographic data including age , sex, location, date of admission and discharge/death, the lab investigations, the imaging, the nature of antibiotics, duration of antibiotics, local complications, organ failure, positive culture reports and duration of hospital stay were recorded in structured proforma. The study group was divided into two groups on the basis of antibiotic used carbapenem Vs noncarbapenem group. Both groups were compared for organ failure, end result death or discharge, duration of discharge.

RESULT & DISCUSSION:

There are 55 patients with severe pancreatitis out of 400 patients with pancreatitis. In the study group the male sex was the predominantly affected 52/55(95%) and most of study population were young. Out of 55 patients 22 patients were given carbapenem antibiotics and rest were given non carbapenem antibiotics which comprises of cephalosporins, fluoroquinolones, Piperacillin +tazobactum, Metronidazole. In the carbapenem group 20 patients were initially on cephalosporins and later they were started on carbapenem as they were not improving. In these 20 patients, renal failure is observed in 14 patients and respiratory failure in 6 patients. All these 20patients survived and they stayed in hospital for 3-5weeks. Two patients in carbapenem group died and they had renal and respiratory failure even they were started on carbapenem in the first week. These two patients stayed in hospital for 3weeks.

Figure: An autopsy specimen consisting of the stomach (A), spleen (B), pancreas (D), and adjacent fat (C) reveals acute inflammation. The pancreas is swollen and hyperemic. Focal areas of green necrosis are present. Small foci of bright yellow, fat necrosis are present. The stomach is folded back so as to reveal its posterior wall and the pancreas.

A total of 33 patients were given non carbapenem antibiotics. Out of 33patients 16patients had renal failure and 12patients had multiorgan failure. 8patients had local complications in form of multiple fluid collections and necrosis more than 50%. 22out of patients received cefaperazone+sulbactum with Fluoroquinolones. 7 patients received only Piperacillin+Tazobactum with Fluoroquinolones. 4 patients received only Fluoroquinolones. 30patients who were on cephalosporins stayed 2-3weeks and all 30 patients improved and were discharged. 3 Patients out of 33 died in the first week due to multiorgan failure.

Table: The demographic and comparative data:

SDP		ADP		D Vs Di		LSH		CAPP		CVC		NCAPP		CVNC		CAPP
Sex	N= 55	Age	N= 55	D / Di	N= 55	Days	N= 55	A	N= 22	OF	N= 22	A	N=33	OF	N= 33	A	%P
Males	52	10-20 yrs	5	D	5	1-10	5	Car	22	RF	14	Cep	33	OF	3	Cep	95
Females	3	20-30 yrs	20	Di	50	10-20	28	Cep	19	RPF	6	Flu	26	RPF	5	Flu	40
Total	55	30-40 yrs	12	Total	55	20-30	17	Flu	17	MOF	2	Met	10	MOF	3	Car	87
		40-50 yrs	13			30-40	5	Met	6					LC	22	Met	29
		50-60 yrs	4
		60-70 yrs	1

Abbreviation details:

SDP= Sex Distribution of study population, N= No. of patients, ADP= Age Distribution of Study Population, D Vs Di= Death Vs Discharge, LSH= Length of stay in the hospital, CAPP= Carbapenem Antibiotics Prescription pattern, A= Antibiotics, Car= Carbapenem, Cep= Cephalosporins, Flu= Fluoroquinolones, Met= Metronidazole, CVC= Comparison of variables in Carbapenem, OF= Organ Failure, RF= Renal failure, RPF= Respiratory failure, MOF= Multi organ failure, NCAPP= Non- Carbapenem Antibiotics Prescription Pattern, CVNC= Comparison of variables in Non- Carbapenem, LC= Local complications, CAPP= Choice of Antibiotics Prescription Pattern, %P= % Prescribed.

CONCLUSION:

Cefaperazone sulbactum is a good first choice antibiotic which is more cost effective than imipenem but with similar efficacy. In India as the most patients belong to low socioeconomic status, it should consider the cefaperazone sulbactum as the first choice and reserve carbapenem antibiotics for non responders to cefaperazone sulbactum. From this observational study concluded that cefaperazone sulbactum along with quinolone is a good first choice antibiotic and reserve the imipenem for sicker and non responders to cephalosporins. It was observed that cefaperazone sulbactum is first choice antibiotic in patients with acute severe pancreatitis and reserve Imipenem for more sicker and non responders to cefaperazone sulbactum.

REFERENCES:

1. Bradley EL 3rd. A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. Arch Surg. May 1993;128(5):586-90.

2. Sommermeyer, Lucille (December 1935). "Acute Pancreatitis".American Journal of Nursing Io (Philadelphia, PA: Lippincott Williams & Wilkins) 35 (12): 1157–1161.

3. Banks P, Freeman M (2006). "Practice guidelines in acute pancreatitis". Am J Gastroenterol 101 (10): 2379–400.

4. Baron TH, Morgan DE. Acute necrotizing pancreatitis. New Engl j Med 1999; 340:1412-17.

5. AGA Institute medical position statement on acute pancreatitis. Gastroenterology 2007; 132:2019-21.

6. Smith R, Southwell-Keely J, Chesher D (2005). "Should serum pancreatic lipase replace serum amylase as a biomarker of acute pancreatitis?” ANZ J Surg 75 (6): 399–404.

7. Scaglione M, Casciani E, Pinto A, Andreoli C, De Vargas M, Gualdi GF (2008). "Imaging assessment of acute pancreatitis: a review". Semin Ultrasound CT MR 29 (5): 322–340.

8. Johnson CD, Abu-Hilal M. Persistent organ failure during the first week as a marker of fetal outcome in acute pancreatitis. Gut 2004; 53:1340.

9. Arvanitakis M, Koustiani G, Gantzarou A, Grollios G, Tsitouridis I, Haritandi-Kouridou A, Dimitriadis A, Arvanitakis C (2007). "Staging of severity and prognosis of acute pancreatitis by computed tomography and magnetic resonance imaging-a comparative study". Dig Liver Dis. 39 (5): 473–482.

10. Bhatia M, Wong FL, Cao Y, et al. Pathophysiology of acute pancreatitis. Pancreatology 2005; 5:132-44.

11. Beger HG, Rau B, Mayer J, Pralle U. Natural course of acute pancreatitis. World J Surg 1997; 21:130-5.

12. Sheehy TW. Acute Alcoholic Pancreatitis. Continnuing Education. 1980:87-88, 92-3, 97-100,105,107,109.

13. Isenmann R, Rau B, Beger HG. Early severe acute pancreatitis: characteristics of a new subgroup. Pancreas 2001; 22:274.

14. Wu BU, Johannes RS, Sun X, et al. The early prediction of mortality in acute pancreatitis: a large population –based study. Gut 2008; 57:1698.

15. Simchuk EJ, Traverso LW, Nukui Y, Kozarek RA .Computed tomography severity index is a predictor of outcomes for severe pancreatitis. Am j Surg 2000; 179:352.

Received on 30.07.2012

Modified on 06.08.2012

Accepted on 09.09.2012

Research J. Pharmacology and Pharmacodynamics. 4(6): November –December 2012, 349-352

A Study on Clinical Profile of Patients with Acute Severe Pancreatitis on Carbapenem versus Non-Carbapenems

Figure: CT scan In Acute Pancreatitis