Intra-abdominal Infections Educational Module

Intra-abdominal Infections Educational Module Developed by: Miranda So, BScPhm PharmD with contributions from the CAHO ASP Project Team

Antimicrobial Stewardship Program (ASP) in Intensive Care Units (ICU) ARTIC Project

Intra-abdominal Infections Educational Module Developed by: Miranda So, BScPhm PharmD “Getting patients the right antibiotics, when they need them”

SCENARIO

CM, a 70-year-old male was recently diagnosed with colon cancer and underwent resection surgery. He received 2 doses each of cefazolin and metronidazole as perioperative antibiotic prophylaxis and was transferred to the surgical ward. On post-op day 5, CM deteriorated clinically (see Table 1) and required increased analgesia. Based on clinical assessment and abdominal CT, anastomotic leak was suspected and he returned to the OR for further resection and re-creation of an end-to-end anastomosis. Stool contamination in the peritoneum was noted during the procedure. He is to be admitted to the ICU post-op on vasopressors. Total parenteral nutrition is due to start the next day. At present, the ICU team is conferring with the surgical team on the most appropriate antibiotic regimen. CM has no known drug allergies and admission screening for methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE) were negative. Table 1: Lab Values and Vital Signs on Post-Op Day 5 (before returning to the OR)

BP (mmHg) 110/60 on vasopressors Temp (C) 38.5 HR (BPM) 80 WBC (counts/L) 12.5x10^9/L SCr (micromole/L)

170

Lactic acid (millimol/L)

2.0

Microbiology (resulted on Day 2 of ICU Admission): Peritoneal fluid: mixed, heavy growth

2 | INTRA-ABDOMINAL INFECTIONS EDUCATIONAL MODULE Developed by: Miranda So, BScPhm PharmD | June 2012


KEY MESSAGES

Source control is an important determinant of outcome in IAI. Choice of empiric antibiotic therapy depends on they type of IAI, while taking into account the

patient’s prior antibiotic exposure and risk of acquiring resistant organisms. For healthcare-associated IAI, patient’s institutional length-of-stay and local (institutional)

susceptibility data should be cosidered in determining empiric antibiotic therapy. Duration of therapy is influenced by achievement of source control. It should be no longer than 3-7

days if source control is achieved and patient is improving clinically. Lack of clinical improvement should prompt further investigation for source of infection, rather than

prolonged antimicrobial therapy. BACKGROUND

Peritonitis is a bacterial infection within the peritoneum of the abdominal cavity. Primary peritonitis (e.g. spontaneous bacterial peritonitis) is an infection that arises in the absence of a gastrointestinal (GI) breach1. The more common secondary peritonitis (focus of this module) usually follows a perforation of the GI tract, which leads to contamination by gut flora into the sterile cavity1. Intra-abdominal infections (IAI) encompass a wide variety of pathological conditions, and are often subcategorized. Below is a list of key definitions.2,3

Uncomplicated IAI: contamination or inflammation does not extend beyond the source and the disease is completely excised at the time of operation. Examples are early traumatic perforation, simple appendicitis and cholecystitis. Complicated IAI: infectious process proceeds beyond the organ that is the source of the infection, and causes localized peritonitis (also referred to as intra-abdominal abscesses) or diffuse peritonitis, depending on the host’s ability to contain the process within a part of the abdominal cavity. Community-acquired: examples include gastroduodenal perforations, ascending cholangitis, cholecystitis, appendicitis, diverticulitis with or without perforations, bowel perforations and pancreatitis in patients without previous surgical intervention or hospitalization.


Healthcare-associated: by definition, are infectious processes that are absent at the time of hospital admission, but become evident 5 or more days after admission. Examples are anastomotic leaks and perforations, and abscesses that develop as a complication of surgery. They may include infections acquired while receiving treatment in other healthcare setting, such as long-term care facilities, dialysis units or surgical day care units, within the previous 12 months. Most importantly, from the perspectives of empiric treatment and antimicrobial stewardship, the choice of empiric antibiotics and their modification should reflect the possibilities of drug-resistant pathogens and acquisition of nosomial organisms. Severity: by definition, IAI that requires ICU admission constitute high-serverity disease. Organ dysfunction (e.g. acute lung injury, renal dysfunction), and signs and symptoms of shock may be present. Patients may be elderly, with extensive comorbidities or immunocompromised state. Acute Physiologic and Chronic Health Evaluation II (APACHE II) score can be used for stratification of patients: low-to-moderate severity (score lower than 15); high severity (score 15 or greater). Control of the source of infection is an important determinant of outcome, and can be achieved either by surgical (e.g. resection) or non-surgical means (e.g. CT-guided percutaneous drainage of abscesses).4 Antimicrobial therapy plays an integral role in IAI management, especially in critically ill patients, as inappropriate empiric therapy is strongly associated with unfavourable outcomes. [See Pharmacotherapy] CLINICAL PRESENTATION2,5,6

Abdominal pain, which may be aggravated by motion or respiration o Decreased intensity and extent of pain with time may suggest localization of the

inflammatory process

Epigastric pain may be associated with peptic ulcer rupture Constitutional symptoms (e.g. anorexia, fever, chills, rigors, night sweats) Nausea, vomiting, diarrhea/constipation Muscle rigidity (“guarding”) of abdominal wall due to peritonitis Decreased or absent bowel sounds Signs and symptoms of sepsis and septic shock due to progression of IAI (refer to “Sepsis”

Module)


tudies: ay reveal bowel distension, obstruction, free air (esp. CXR showing free air

d

Imaging so X-ray—m

under the diaphragm) o Ultrasound—frequently the initial step in evaluating IAI; can also guide drainage of flui

collections/abscesses o Computerized tomography (CT)—apart from detecting intra-abdominal processes; can

also guide fluid collections/abscesses

Cultures eritoneal fluid sampling is more likely to give modifying information in healthcare-

n

o

TIOL GY

tis tends to be polymicrobial. In community-acquired IAI, especially during the early

.

o Passociated IAI or severely ill patients. In early community-acquired IAI, they are oftenot available. Blood cultures are not clinically relevant in community-acquired IAI, but may add diagnostic information to healthcare-associated infections. Obtained only if the diagnosis of IAI is unclear or if there is a high suspicion of bacteremia.

E O

Secondary peritonistage, the pathogens are closely related to the normal microflora of the GI tract. In the stomach, there are few organisms that cause peritonitis (although pH-altering therapy can modify this). Both volume and variety of bacterial species increase progressively from the duodenum to the ileum, dominated by streptococci, lactobacilli and Enterobacteriaceae (enteric gram negative bacilli).3 In the colon, bacteria load is very high [109 to 1011 colony forming unit (cfu)/g], dominated by obligate anaerobes (Bacterioides spp.; Clostridium spp.; non-spore forming gram-positive bacilli) and EnterobacteriaceaeTherefore in community-acquired IAI without previous exposure to antibiotics, the microbial causes of the infection are relatively predictable.

ore pathogens:C 3

Streptoccocus spp.* nteric gram negative bacilli) (e.g. E coli*, Klebsiella spp., Proteus spp., Enterobacteriaceae (e

Serratia marcescens) Anaerobes (e.g. B. fragilis*, non-fragilis Bacteroides, Clostridium spp., Fusobacterium spp.,

Lactobacillus spp., Peptostreptococcus spp., Veillonella spp.)


*top three most frequently isolated ealth-care associated IAI, the etiology is influenced by the patiIn h ent’s prior antibiotic exposure

n risks (e.g. institutional length of stay). Therefore, in addition to d:

(selection pressure) and colonizatiocore pathogens, coverage against drug-resistant and nosocomial organisms should be considere

More difficult to treat gram-negative bacilli (e.g. Pseudomonas aeruginosa) Drug-resistant gram-negative bacilli (e.g. extended-spectrum beta-lactamase-producing (ESBL) E

coli or K pneumoniae; ampC-producing gram-negative bacilli ) Enterococcus spp. Methicilin-resistant S. aureus (MRSA) in colonized patients ) [see Empiric Antifungal Therapy]

Empiric therapy should be directed against core pathogens in community-acquired IAI. Additional gainst resistant organisms or non-core pathogens as described above should be

onsidered in healthcare-associated infections and in patients with high severity IAI, taking into

with

Candida spp. (yeast PHARMACOTHERAPY

EMPIRIC

coverage acaccount local antibiogram in the selection of treatment options. Broadening of coverage is recommended due to the high risk of mortality and morbidity in severely ill patients and thosehealthcare-associated infections, leaving little margin for error in this patient population.

Selection of Antibiotics Type of Examples IAI Spectrum of

coverage Recommended regimen

Alternative for Penicillin-allergic patients

Community-a uncomplicated: cquired and No perforation

ted appendicitis, operated , Non-perfora Enteric gram

negative bacillianaerobes

Perforation Perforations of stomach/ without established infection

s operated on within 12-24 hrs

duodenum, traumatic bowel perforation

Gram-positive cocci, facultative and obligate anaerobes

Cefazolin + metronidazole Gentamicin + metronidazole


Selection of Antibiotics Type of IAI

Examples Spectrum of coverage

Recommended regimen

Alternative for Penicillin-allergic patients

Community-acquired, complicated Mild to moderate severity

Perforated appendicitis, perforated diverticulitis

Enteric gram negative bacilanaerobes

li, Cefazolin + metronidazole

High severity

Shock, new organ failure, ICU admission

Enteric gram-negative bacilli, anaerobes, may

cocci include enteroOther risk factors for

entreatmfailure

t or

d

Ceftriaxone + metronidazole;

ta on severity of illness

Gentamicin + metronidazole

Age >70; immunosuppression; pobaseline nutrition; delayed or inadequate source control

Enteric gram-negative bacilli, anaerobes; enterococci in theimmunosuppresse

consider piperacillin-

zobactam based

Health-care associated Mild-to-moderate

Hospitalized anastomotic leak, post-op abscess

≥5d; Pipertazo

mild severity or minimal prior

Resistant gramnegative bacilli including P. aeruginosa; anaerobes; enterococci

- acillin-bactam;

consider ceftriaxone + metronidazole if

exposure to antibiotics

High severity tic leak; shock;

ICU admission lli

SBL-e

bacilli; anaerobes; i are

ogens

Hospitalized ≥5d; anastomo

Resistant gram-negative baciincluding P. aeruginosa, Egram-negativ

enterococci

Piperacillin-tazobactam; carbapenem$ if ESBL-gram-negative bacillpotential path

Other riskfactors fo

r

healthcare-associated infection

ty;

re

Vancomycin + gentamicin + metrondazole OR carbapenem¶ (meropenem or

imipenem) + vancomycin

Nursing home; rehab facilidialysis patient; recent antibiotic exposu

Resistant gram-negative bacilli, enterococci

Pipericillin-tazobactam; consider ceftriaxone+ metronidazole if mild severity

Biliary Tract Mild-to-moderate

Enteric gram negative bacilli

Cefazolin Gentamicin

High severity

Ascending cholangitis; acute calculous cholecystitis

Enteric gram negative bacilli, enterococci

Gentamicin + vancomycin Ceftriaxone +ampicillin

A Best Practice in General Surgery Guideline #4 Managem minal Infections2

$ : enteroc udomonas sp. but is active against ESBL-producing g ve ¶ s-r llin and onsidered to be ≤1%.

dapted from: nem

ent of Intra-AbdoCarbaperam-negatiRisk of cros

note ertapenem does not havebacilli. eactivity between penici

activity against

carbapenem is c

occi or Pse


Biliary tract infections:2,6

All patients with ascending cholangitis should receiv ial th cute calculous cholecystitis should receive antimicrobial therapy if there is an increased likelihood of

atients with acute cholecystitis taken to the operating room should receive antibiotic o further antibiotics are required

complicated cholecystitis characterized by perforation, gangrene or antimicrobial therapy may be assessed based on achievement of source

ations

e antimicrob erapy. Patients with a

bactibilia (fever, leukocytosis, advanced age, immunosuppression or diabetes) or suspicion of superimposed infection (adjacent abscess, air in gallbladder wall or lumen, or suspicion of perforation). All pprophylaxis prior to skin incision. In uncomplicated cholecystitis, nafter cholecystectomy. Inempyema, duration of control [see Duration of Therapy]. As for coverage, the empiric antibiotic regimen should be active against Enterobacteriaceae. Consideration fo enterococcal coverage should be given in high-severity infections [see Modificto Empiric Therapy]. In patients with mild-to-moderate infections, enterococcal activity is not required.Anaerobic activity is not indicated unless a biliary-enteric anastomasis is present. Of note, liver transplant recipients with ascending cholangitis are at high risk of enterococcal infection. Only patients with biliary–enteric anastomoses require anaerobic coverage, such as metronidazole. Modifications to Empiric Therapy Against Core Pathogens: Anti-enterococcal therapy: Enterococci may be isolated from intra-operative specimens (incidence ~20%),7 but targeted therapy is generally not necessary in mild-to-moderate community-acquired IAI. Regimens with anti-enterococcal activity have not been shown to make a difference in outcomes compared to thoslack anti-enterococcal activity.

e that

are-associated IAI, positive intra-e outcomes. Risk factors associated with

3,6,8,9 In critically ill patients with severe community-acquired and healthcabdominal cultures for enterococci are associated with worsenterococcal IAI include:

Recent exposure to cephalosporins Failed initial treatments that lack anti-enterococcal activity Post-operative peritonitis IAI following liver transplant


Severe immunosuppression Patients with peritonitis and valvular heart disease or prosthetic intravascular device may be at

risk of infective endocarditis cause by Enterococci spp. efore require empiric regimens with anti-enterococcal activity.

ram-Negative Bacilli:

Patients with these risk factors may ther Anti-Pseudomonal Therapy and Coverage Against Resistant G

age and/or antibiotic against resistant gram-negative bacilli is not c d, mild-to-moderate IAI.

sev I, empiric coverage against multi-drug

entioned, it is also appropriate to provide anti-pseudomonal coverage empirically to those who e section on

e-escalation”).

Routine anti-pseudomonal coverne essary in community-acquire Prior exposure to antibiotics has been shown to be an influencing factor on acquiring resistant-pathogens in patients with IAI.10 Importantly, in critically ill, haemodynamically unstable patients with

ere community-acquired IAI or healthcare-associated IAresistant pathogens, including against P. aeruginosa, is reasonable (see also “Etiology”.) As mfailed initial therapy that lacked anti-pseudomonal activity, pending culture results (se“D Empiric antifungal therapy: In critically ill patients, invasive candidiasis is associated with significant mortality in healthcare-associated or post-op IAI, and in immunocompromised patients. Risk factors1,11,12

Yeast in peritoneal fluid Severe IAI (APACHE score 15 or greater) Female IAI of upper GI origin Intra-operative cardiopulmonary failure (e.g. shock) Recent prior exposure to antibiotics ultiple cM olonization sites Recurrent perforations


Antifungal treatment with fluconazole (IV or oral) should be initiated if yeast is isolated from r Echinocandins (anidulafungin, caspofungin, micafungin) are alternatives

nt Candida spp. are common within the particular institution or if the patient f peritonitis. Although early/pre-emptive

duce risk of candidemia or invasive candidiasis, it has not nd therefore remains controversial.13 In addition, the risk of

yeast due to fluconazole overuse should be not be overlooked.

ARGETED

nd ulture results both reflect a pure monomicrobial infection).

E-ESCALATION

nt to

in

URATION OF THERAPY

rom an antimicrobial stewardship perspective, emergence of drug-resistant pathogens in the patient at may be

int aoperative specimens.empirically if azole-resistawas already on azole therapy prior to the development oantifungal therapy has been shown to rebeen shown to impact overall mortality, aemergence of less susceptible T IAIs are often polymicrobial in their etiology, and while anaerobes are important pathogens, they areoften difficult to culture in the microbiology laboratory, since they would require specialized environment and handling. It is not uncommon to see “mixed growth” reported from peritoneal specimens, which likely reflect the GI tract flora, especially in community-acquired IAI. Therefore therapy should target known pathogens if available, however, spectrum of activity should be maintained against core pathogens even if only one species is isolated (unless the Gram stain ac D Pseudomonas aeruginosa is not normal GI tract commensal flora. However, it may be an opportunistic pathogen when there is a disruption to normal flora, e.g. in patients who had receexposure to antibiotics or underwent bowel surgery. If modifications were made to empiric therapyinclude anti-pseudomonal activity in a critically ill patient, but P. aeruginosa was not identifiedperitoneal (or blood) specimens, it is reasonable to discontinue antipseudomonal coverage. D Fand in an institution’s antibiogram, as well as C. difficile infections are collateral damage thattributed to overuse of antibiotics.1 Evidence is increasing that prolonged antibiotic therapy is unnecessary in IAI.14-16 Rather, duration of therapy is dependent on achievement of source control:2

Uncomplicated community IAI, such as non-perforated appendicitis, only requires antibiotics for

surgical prophylaxis


Perforations that were operated on within 12-24 hrs may be treated with a 24-hr course of antibiotics

In complicated IAI and healthcare-associated IAI, duration of therapy may be 3-7d after achievement of source control, provided that patient is clinically stable with signs of clinical resolution (e.g. normalization of white blood cell count; absence of fever; return of bowel function)

In patients who do not demonstrate improvement, re-assessment for the need for source control should be made at 4-7d for ongoing infection (e.g. diagnostic imaging), rather than prolonging the

(For established candidemia, refer to “Candidemia” module.)

1. 2.

http

course of antibiotics.

REFERENCES

Mazuski JM and Solomkin JS. Intra-abdominal infections. Surg Clin N Am 2009;89: 421–437. Doyle J, Nathens A, Morris A, Nelson S and McLeod M. Best Practice in General Surgery

Guideline #4: Management of Intra-abdominal Infections. Available at ://generalsurgery.utoronto.ca/Assets/GenSurgery+Digital+Assets/IAI.pdf (accessed June 6, 2). 201

, Harding GKM et al. Canadian practice 11-37.

. Sartelli M, Viale P, Koike K, Pea F, Tumietto F, van Goor H, et al. WSES consensus for first-line management of intra-abdominal infections. World Journal of 1;6:2.

the

of

errington J, et al. Randomized controlled trial of moxifloxacin compared with piperacillin-tazobactam and amoxicillin-clavulanate in the treatment of complicated intra-abdominal infections. Ann Surg 2006;244(2):204-11.

3. Chow AW, Evans GA, Nathens AB, Gall CG, Hansen Guidelines for surgical intra-abdominal infections. Can J Infect Dis Med Microbiol 2010;21:g

4conference : GuidelinesEmergency Surgery 2015. Mandell, Douglas, and Bennett's principles and practice of infectious diseases / [edited by] Gerald L. Mandell, John E. Bennett, Raphael Dolin.—7th ed. 2009. Philidelphia, PA. Churchill Livingstone Elsevier. 6. Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJC, Baron EJ et al. Diagnosis and Management of Complicated Intra-abdominal Infection in Adults and Children: Guidelines bySurgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010; 50:133–64.7. Montravers P, Lepape A, Dubreuil L, Gauzit R, Pean Y, Benchimol D et al. Clinical and microbiological profiles of community-acquired and nosocomial intra-abdominal infections: resultsthe French prospective, observational EBIIA stuyd. J Antimicrob Chemother 2009;63: 785-94. 8. Malangoni MA, Song J, H


9. Solomkin JS, Yellin AE, Rotstein OD et al. Ertapenem versus piperacillin-tazobactam in the treatment of complicated intraabdominal infections, results of a double-blind, randomized compPhase III trial. Ann Sur

arative g 2003;23792):235-45.

uid be predicted in intensive care unit patients with peritonitis? Crit Care Med. 2003

ritically

erapy after emergency

tronidazole-fosfomycin

10. Seguin P, Laviolle B, Chanavaz C, et al. Factors associated with multi-drug resistant bacteria in secondary peritonitis: impact on antibiotic therapy. Clin Microbiol Infect 2006;12:980-5. 11. Dupont H, Bourichon A, Paugam-Burtz C, Mantz J, Desmonts JM. Can yeast isolation in peritoneal flMar;31(3):752-7. 12. Eggimann P, Francioli P, Bille J et al. Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical pateitns. Crit Care Med 1999;27:1066-72. 13. Shorr A, Chung K, Jackson WL, Waterman PE, Kollef MH. Fluconazole prophylaxis in cill surgical patients: a meta-analysis. Crit Care Med 2005;33:1928-35. 14. Schein M, Assalia A, Bachus H. Minimal antibiotic thabdominal surgery: a prospective study. Br J Surg 1994;81:989–91. 15. Andåker L, Höjer H, Kihlström E, et al. Stratified duration of prophylactic antimicrobial treatment in emergency abdominal surgery. Mevs. metronidazole-gentamicin in 381 patients. Acta Chir Scand 1987;153:185–92. 16. Basoli A, Chirletti P, Cirino E, et al. A prospective, double-blind, multicenter, randomized trial comparing ertapenem 3 vs. R5 days in community-acquired intraabdominal infection. J Gastrointest Surg 2008;12:592–600.

Documents

Intra-abdominal Infections Educational Module