Empiric Antimicrobial therapy for different types of Gall bladder pathologies based on

Bacterial etiology

S.Rohra**, KP Balsara*, AA Poojary**, Vardhini W*, T.E.Udwadia*, N.Doctor*, K.Kapadia

*Dept of Surgery **Dept. of Pathology & Microbiology

Breach Candy Hospital Trust

Introduction

Laura M. Stintont et al, Gut and Liver, Vol. 6, No. 2, April 2012, 172-187

Introduction

Symptomatic Cholelithiasis - Cholecystectomy

Bactobilia 20 - 46 %

Varies with different gall bladder pathologies

Relation ship between bactobilia, wound infection and post operative wound complication

Post-operative wound infection 7-20 %

Mohammad Moazeni-Bistgani, et al. Acta Medica Iranica, 2013; 51(11): 779-783 A Suri, et al. The Internet Journal of Surgery Volume 22 Number 2 Vasitha Abeysuriya, et al. Hepatobiliary Pancreat Dis Int 2008; 7: 633-637 Faraz Ahmad,et al . International Journal of Scientific Study | July 2014 | Vol 2 | Issue 4

Objective of the study

To identify aerobic & anaerobic bacteria in patients with gall bladder disease

Perform susceptibility tests

Formulate an empiric policy for antimicrobials agents

Ethics & Disclosures

The study was approved by the Institutional Review Board & the Ethics Committee at Breach Candy Medical Research Center (BCMRC)

Grant for conducting the study was given by BCMRC

Inclusion Criteria

All cases where cholecystectomy was performed for gall bladder disease due to any cause

Diagnosis of cholecystitis

1. Acute Cholecystitis was diagnosed by

Clinical evaluation

WBC count >10,000

elevated CRP

USG/ CT scan / MRCP

CBD stones diagnosed on MRCP / ERCP

2. Acalculous cholecystitis was diagnosed when inflammatory existed without stones

3. Chronic cholecystitis, when pts. had recurrent attacks of pain and imaging was s/o of chronic disease

Material and Methods

Prospective study: April 2014 to May 2015

Samples accepted : Bile

Pus

Swab

Demographic and clinical details of the patient was recorded

from GB

Materials and Methods

Aerobic culture

Specimens were inoculated onto 5% sheep blood, chocolate and MacConkey agar plates for aerobic and facultative organisms.

The plates were incubated aerobically (MacConkey agar) or under 5% C02 (5% sheep blood and chocolate agars) at 37C and examined at 24 and 48 h.

Culture positive samples were processed using the automated Vitek 2 Compact system for identification & susceptibility

Materials and Methods

Anaerobic culture

Specimens were processed on SBA & anaerobic agar

The plates were incubated in anaerobic pouches with reagent & indicator (Merck mini) & anaerobic jars (Merck)

All plates were incubated at 37 C in a CO2 environment and examined at 72 hrs.

For culture positive samples , smear & aero tolerance was performed

Aero tolerance negative cultures were put for identification using the anaerobic (ANC) cards on Vitek 2 Compact

Susceptibility testing were performed using standard methods using Minimal Inhibitory Concentration (MIC) methods

Results & Discussion

Total of 91 specimens were received and processed

50 bile

36 swab from gall bladder

5 pus

Study group : 46 M, 45 F

Mean age : 56.1 yrs.

Results & Discussion

Overall, 42% (38/91) specimens were culture positive

73% (28/71) specimens were monomicrobial

27% (10/38) specimens had >=2 organisms

Isolates

47 aerobic organisms & 2 anaerobic organisms

Anaerobes in 2 pts. Prevotella & Bacteroides sp.

Gram negative bacilli (N=35)

0

5

10

15

20

25

E.coli Klebsiella Enterobacter Kluyvera Serratia

% Susceptibility of Gram Negative Bacilli

21

35

59

38

50

68

56

29

76

74

79

94

82

68

0 10 20 30 40 50 60 70 80 90 100

Ampicillin

Cefuroxime

Cefipime

Ceftriaxone

Amox+ Clav

Cefo+ Sulbactum

Pip+Tazo

Ciprofloxacin

Gentamicin

Amikacin

Ertapenam

Imipenam

Meropenam

Tigecyline

Options for Empiric therapy: Amoxicillin clavulanic acid Gentamicin Piperacillin Tazobactam

Gram Positive Cocci (n= 12)

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

Nu

mb

ers

of

iso

late

s

% Susceptibility of Gram Positive Cocci

0

0

0

50

80

100

100

100

100

100

100

100

50

100

100

100

100

100

0 20 40 60 80 100 120

Ampicillin

Amox+ Clav

Ceftriaxone

Ciprofloxacin

Gentamicin

Linezolid

Tecioplanin

Vancomycin

Tigecycline

Streptococci

Enterococci

Results & Discussion

Clinical diagnosis Nos. AMA (%)

Culture positivity

(%)

Reference

Acute Calculous cholecystitis 56 75 41 32% MR Capoor 2008, Braz J

Infect Dis

Chronic Calculous cholecystitis 13 14 46

Asymptomatic cholelithiasis 10 0 0

With Gangrenous cholecystitis 5 50 80

Associated CBD calculus 3 0 66 52% MR Capoor 2008, Braz J

Infect Dis

With Perforation of GB* 2 100 100

Acalculous cholecystitis 1 0 0

Xanthogranulomatous cholecystitis

1 100 100

Risk Stratification

Type 1 Type 2 Type 3 E.g.

Health Care Contact No Yes Prolonged Hospitalization

Procedures No Minimum

Major invasive Procedures

Invasive bilary procedures,

stenting

Antibiotic Rx History Patients

No in last 90 days No in last 90 days Repeat multiple

antibiotics Oral or IV

Characteristics Young No co-

morbid conditions.

Elderly Few Co-morbid

conditions

Immunocompromised, or with many co-morbid conditions

DM,CKD, immunosuppre

ssion

Causative Pathogen could be

Susceptible to Common narrow

spectrum antibiotics

ESBLs ESBLs / NDM/ VRE

/MRSA

Carmelli Score A.Salvovici et al Therapeutics, Pharmacology & Clinical Toxicology 2009

Limitations of the study

Sample small size

Swabs from gall bladder

Anaerobes specific media

For different pathologies: different rates of bactobilia

Empiric antibiotic : risk stratification

Gram negatives were commonly isolated followed by gram positive and anaerobes.

60% of GNB were ESBL. 20% were Carbapenamase producers

Empiric antibiotic : Local susceptibility pattern

Among Gram positive, Enterococcus outnumbered Streptococci

Empiric antibiotic : common organism associated with disease

Antimicrobial Stewardship Policy

For prophylaxis : Cefazolin/Cefuroxime/Aminoglycosides (single dose)

For empiric therapy:

o Gentamicin o Piperacillin Tazobactam o Amoxicillin clavulanic acid and gentamicin

For de-escalation/targeted therapy:

Based on culture results

Carbapenems should be reserved for critically ill patients

Fluroquinolones no role to play in treatment of biliary pathology