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Lecture 24 Intra-abdominal Infections Lalji INTRA-ABDOMINAL INFECTIONS: Appendicitis (right-sided abd. pain) Peritonitis Intra-abdominal abscess Cholangitis and cholecytitis Diverticuilitis (left-sided abd. pain) C. difficile infection (AAD) Food poisoning/Traveller’s Diarrhea Helicobacter pylori (PUD) PERITONEAL CAVITY: Extends from undersurface of diaphragm to floor of the pelvis Contains stomach, most of small bowel, large bowel, liver, gallbladder and spleen Duodenum, pancreas, kidneys, adrenals are in posterior peritoneum Cavity contains 50 mL sterile serous fluid, low protein, leukocytes, and no fibrinogen NORMAL FLORA: Reside on body surface/cavities, but normally do not invade or cause immune response Prevent colonization, invasion, infection by other organisms Harmless at usual sites, but may produce disease if introduced into other areas that are supposed to be sterile (opportunitists) Understanding the pattern & density of normal flora enables prediction of microbiologic etiology of intra-abdominal infxns NORMAL GI MICROFLORA: Stomach Total bacterial count 0-10 9 log organisms/g H. pylori, streptococci, lactobacilli Upper small intestine Total bacteria count 0-10 5 log organisms/g Aerobes: enterococci, staphylococci, lactobacilli, E. coli, Klebsiella Anaerobes: bacteroides BACTERIAL SYNERGISM: Size of inoculum, number, and types of bacterial species affect outcome Combinations of both aerobes and anaerobes increases risk of infection, and appear to be much more lethal Facultative aerobes set-up environment conducive to anaerobes: o Consume O2 provide anaerobic environment o Produce waste used as nutrients by anaerobes o Produce enzymes that promote anaerobic tissue invasion ABDOMINAL INFECTION: 2-STAGE PROCESS 1. Days 1-5: acute, generalized gram (-) peritonitis, bacteremia, sepsis, high mortality 2. Day 5+: abscess formation, primarily by anaerobes (B. fragilis) PERITONITIS: PATHOGENESIS: After bacteria gain entry to peritoneal cavity, humoral and cellular immune defenses respond o If there a limited number of bacteria, the immune system is able to contain the infection o Under certain conditions, bacteria disseminate throughout peritoneal cavity peritonitis 1. Large bacterial inoculum 2. Continuing bacterial contamination 3. Mixed organisms that are virulent due to synergism With peritonitis, see outpouring of serous fluid containing leukocytes, fibrin, and proteins, which make up exudates on the peritoneal surface, and form adhesions between structures Adhesions and ileus (paralysis of intestines) leads to confinement and collection of fluid which can cause bowel distension Protein-rich fluid draws more water into the peritoneal space, “third spacing” from other compartments, and may lead to hypovolemia and hypotension (worsened with fever, N/V) Inflamed peritoneal membrane permits bacteria and endotoxins to be absorbed into bloodstream and septic shock and death Foreign objects, dead, necrotic tissue have negative effects on immune function If body is successful in localizing contamination, abscess will form o Abscesses are formed by action of inflammatory cells, bacteria, fibrin and contain necrotic tissue, bacteria and WBCs o Abscess environment is anaerobic, hypertonic, acidic, and inhibits the action of antimicrobials PRIMARY PERITONITIS: AKA SPONTANEOUS BACTERIAL PERITONITIS (SBP): Relatively uncommon, but most commonly in pts with chronic liver disease o SBP occurs in 10-25% of ps with ascites related to alcoholic cirrhosis Can also be seen in patients with acute hepatitis, CHF, metastatic malignancy, or lupus (SLE), peritoneal dialysis (PD) Source of bacteria (focus) is outside the peritoneal cavity o Thought to occur by migration of microbes through the GI wall to the mesenteric lymph nodes o Bacteria infect ascitic fluid by hematogenous or lymphatic systems Bacterial translocation can also occur in non-cirrhotic patients whereby bacteria are transported via bloodstream, skin, lymphatics, or fallopian tubes to peritoneal cavity ETIOLOGY: often single organism E. coli 65% K. pneumoniae 15% S. pneumoniae 15% Enterococcus 5% Anaerobes < 1% CLINICAL PRESENTATION: Patient often not in acute distress Fever/chills, vomiting, diffuse abdominal pain, rebound tenderness, guarding, bowel sounds o RLQ pain = appendix; LUQ = pancreas, RUQ = liver or gallbladder May take days to weeks to develop Peritoneal fluid: PMNs (>250/mm 3 ); pH < 7.35; + lactate, protein, gram TREATMENT PRINCIPLES: Usually only requires antibiotics x 5 days, no surgical intervention Primary need to cover E. coli and other gram (-) pathogens Re-check ascitic fluid (repeat parancetesis) at 48 hours o If fluid is sterile, WBC < 250/mm 3 , protein is , and patient is clinically well complete therapy TREATMENT OPTIONS: Ceftriaxone or cefotaxime Alternatives: o Ampicillin (or cefazolin) + gentamicin o Piperacillin/tazobactam o Ertapenem If your hospital has resistant E. coli and K. pneumoniae (ESBL) use: o Imipenem or meropenem o Ciprofloxacin, levofloxacin, moxifloxacin PREVENTION: Prophylactic antibiotics decrease incidence of peritonitis o Not demonstrated to reduce hospitalization or survival rates o Increase carriage of MDR organisms 1 p prophylaxis: CTX 1-2 g daily while NPO, then TMP/SMX 1DS BID, norfloxacin 400 mg BID, or cipro 500 mg BID to complete 7 days 2 o prophylaxis: TMP/SMX 1DS daily, norfloxacin 400 mg daily, ciprofloxacin 500 mg daily for lifetime

Lecture 24 Intra-abdominal Infections Lalji INTRA ... · • Cholangitis and cholecytitis ... • Relatively uncommon, but most commonly in pts with chronic liver disease o SBP occurs

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Page 1: Lecture 24 Intra-abdominal Infections Lalji INTRA ... · • Cholangitis and cholecytitis ... • Relatively uncommon, but most commonly in pts with chronic liver disease o SBP occurs

Lecture 24 Intra-abdominal Infections Lalji

INTRA-ABDOMINAL INFECTIONS:

• Appendicitis (right-sided abd. pain)

• Peritonitis

• Intra-abdominal abscess

• Cholangitis and cholecytitis

• Diverticuilitis (left-sided abd. pain)

• C. difficile infection (AAD)

• Food poisoning/Traveller’s Diarrhea

• Helicobacter pylori (PUD)

PERITONEAL CAVITY:

• Extends from undersurface of diaphragm to floor of the pelvis

• Contains stomach, most of small bowel, large bowel, liver, gallbladder and spleen

• Duodenum, pancreas, kidneys, adrenals are in posterior peritoneum

• Cavity contains 50 mL sterile serous fluid, low protein, leukocytes, and no fibrinogen

NORMAL FLORA:

• Reside on body surface/cavities, but normally do not invade or

cause immune response

• Prevent colonization, invasion, infection by other organisms

• Harmless at usual sites, but may produce disease if introduced

into other areas that are supposed to be sterile (opportunitists)

• Understanding the pattern & density of normal flora enables

prediction of microbiologic etiology of intra-abdominal infxns

NORMAL GI MICROFLORA:

Stomach Total bacterial count 0-109 log organisms/g

• H. pylori, streptococci, lactobacilli

Upper small intestine

Total bacteria count 0-105 log organisms/g

• Aerobes: enterococci, staphylococci, lactobacilli, E. coli, Klebsiella

• Anaerobes: bacteroides

BACTERIAL SYNERGISM:

• Size of inoculum, number, and types of bacterial species affect outcome

• Combinations of both aerobes and anaerobes increases risk of infection, and appear

to be much more lethal

• Facultative aerobes set-up environment conducive to anaerobes:

o Consume O2 provide anaerobic environment

o Produce waste used as nutrients by anaerobes

o Produce enzymes that promote anaerobic tissue invasion

ABDOMINAL INFECTION: 2-STAGE PROCESS

1. Days 1-5: acute, generalized gram (-) peritonitis, bacteremia,

sepsis, high mortality

2. Day 5+: abscess formation, primarily by anaerobes (B. fragilis)

PERITONITIS:

PATHOGENESIS:

• After bacteria gain entry to peritoneal cavity, humoral and cellular immune defenses respond

o If there a limited number of bacteria, the immune system is able to contain the infection

o Under certain conditions, bacteria disseminate throughout peritoneal cavity peritonitis

1. Large bacterial inoculum

2. Continuing bacterial contamination

3. Mixed organisms that are virulent due to synergism

• With peritonitis, see outpouring of serous fluid containing leukocytes, fibrin, and proteins, which make up exudates on the peritoneal surface, and form

adhesions between structures

• Adhesions and ileus (paralysis of intestines) leads to confinement and collection of fluid which can cause bowel distension

• Protein-rich fluid draws more water into the peritoneal space, “third spacing” from other compartments, and may lead to hypovolemia and hypotension

(worsened with fever, N/V)

• Inflamed peritoneal membrane permits bacteria and endotoxins to be absorbed into bloodstream and septic shock and death

• Foreign objects, dead, necrotic tissue have negative effects on immune function

• If body is successful in localizing contamination, abscess will form

o Abscesses are formed by action of inflammatory cells, bacteria, fibrin and contain necrotic tissue, bacteria and WBCs

o Abscess environment is anaerobic, hypertonic, acidic, and inhibits the action of antimicrobials

PRIMARY PERITONITIS:

AKA SPONTANEOUS BACTERIAL PERITONITIS (SBP):

• Relatively uncommon, but most commonly in pts with chronic liver disease

o SBP occurs in 10-25% of ps with ascites related to alcoholic cirrhosis

• Can also be seen in patients with acute hepatitis, CHF, metastatic

malignancy, or lupus (SLE), peritoneal dialysis (PD)

• Source of bacteria (focus) is outside the peritoneal cavity

o Thought to occur by migration of microbes through the GI wall to

the mesenteric lymph nodes

o Bacteria infect ascitic fluid by hematogenous or lymphatic systems

• Bacterial translocation can also occur in non-cirrhotic patients whereby

bacteria are transported via bloodstream, skin, lymphatics, or fallopian

tubes to peritoneal cavity

ETIOLOGY: often single organism

• E. coli 65%

• K. pneumoniae 15%

• S. pneumoniae 15%

• Enterococcus 5%

• Anaerobes < 1%

CLINICAL PRESENTATION:

• Patient often not in acute distress

• Fever/chills, vomiting, diffuse abdominal pain, rebound tenderness,

guarding, ↓ bowel sounds

o RLQ pain = appendix; LUQ = pancreas, RUQ = liver or gallbladder

• May take days to weeks to develop

• Peritoneal fluid: ↑ PMNs (>250/mm3); pH < 7.35; + lactate, protein, gram

TREATMENT PRINCIPLES:

• Usually only requires antibiotics x 5 days, no surgical intervention

• Primary need to cover E. coli and other gram (-) pathogens

• Re-check ascitic fluid (repeat parancetesis) at 48 hours

o If fluid is sterile, WBC < 250/mm3, protein is ↓, and patient is

clinically well complete therapy

TREATMENT OPTIONS:

• Ceftriaxone or cefotaxime

• Alternatives:

o Ampicillin (or cefazolin) + gentamicin

o Piperacillin/tazobactam

o Ertapenem

• If your hospital has resistant E. coli and K. pneumoniae (ESBL) use:

o Imipenem or meropenem

o Ciprofloxacin, levofloxacin, moxifloxacin

PREVENTION:

• Prophylactic antibiotics decrease incidence of peritonitis

o Not demonstrated to reduce hospitalization or survival rates

o Increase carriage of MDR organisms

• 1p prophylaxis: CTX 1-2 g daily while NPO, then TMP/SMX 1DS BID,

norfloxacin 400 mg BID, or cipro 500 mg BID to complete 7 days

• 2o prophylaxis: TMP/SMX 1DS daily, norfloxacin 400 mg daily,

ciprofloxacin 500 mg daily for lifetime

Page 2: Lecture 24 Intra-abdominal Infections Lalji INTRA ... · • Cholangitis and cholecytitis ... • Relatively uncommon, but most commonly in pts with chronic liver disease o SBP occurs

Lecture 24 Intra-abdominal Infections Lalji

PERITONITIS (CONTINUED):

PD-RELATED PERITONITIS:

PD-RELATED PERITONITIS:

• Source of bacteria (focus) is outside the peritoneal cavity

• 60% of all patients on chronic ambulatory peritoneal dialysis (CAPD) will

have at least one episode in 1st year

• Average incidence in CAPD patients is 1.3 – 1.4 eps/year

• Catheter connecting abdominal cavity to exterior body is a major risk factor

• Submit first cloudy effluent to lab for gram stain & culture

ETIOLOGY:

• S. epidermis 8%

• S. aureus 4%

o More likely if nasal carrier, immunocompromised, or diabetic

• Enterobacteriacae 3%

TREATMENT PRINCIPLES:

• Empiric therapy should cover both gram + organisms (with

vancomycin if there is a lot of MRSA or cefazolin) and gram –

organisms (with 3rd/4th gen cephalosporins or aminoglycosides)

• Can use intra-peritoneal (IP) or intra-venous (IV)

o IP is preferred due to high local concentrations: can be

dosed intermittently or continuous dosing

• Total duration is at least 2 weeks

o Sometimes 3 weeks if severe infections and those with

P. aeruginosa or S. aureus

• Narrow therapy when C&S results are back

• High relapse rate, watch for abscess, consider catheter removal

(esp. if keep having repeat infections with same pathogens)

TREATMENT OPTIONS:

• IP > IV

o Cefazolin 15 mg/kg IP + gentamicin 0.6 mg/kg IP once per day (6 hours dwell time) synergistic combination

o Vancomycin 15-30 mg/kg IP q7days + gentamicin 0.6 mg/kg IP once per day

o May also use IV vancomycin or cefazolin, as well as the IP

• Instead of AMG, can use ceftazidime, cefepime, carbapenem

o Use of cefazolin + ceftazidime NOT optimal as the 2 beta-lactams are antagonistic promotes resistance

o Ciprofloxacin no longer recommended due to high resistance plus not active for Staph

SECONDARY PERITONITIS:

BACKGROUND:

• Source of bacteria (focus) is within the peritoneal

cavity, usually from the GIT

o Bowel perforation trauma OR neoplasms,

mechanical problems

o Ruptured appendix

• Often complicated with abscess

o Harder to treat infection

o Often need to control source through surgery

and drain abscess

ETIOLOGY:

• Microbiologic etiology depends on location of infection, but is commonly polymicrobial

Gram-negative bacilli Anaerobes

• E. coli 71%

• Klebsiella sp 14%

• P. aeruginosa 14%

• Proteus spp. 5%

• B. fragilis 35%

• Other bacteriodes spp. 71%

• Prevotella 12%

• Peptostreptocci 17%

• Clostridium spp. 29%

• Fusobacterium spp. 9% Candida may be present

Gram-positive cocci

• Enterobacter spp. 5%

• Streptococci (incl. Enterococci) 12-38%

• Staphylococci 4%

RISK FACTORS ASSOCIATED WITH MORTALITY:

• Age > 70 years

• Comorbid conditions

o Renal/liver disease

o Malignancy

• Immunocompromised

• Severe illness (i.e. sepsis)

• Diffuse peritonitis/extensive peritoneal involvement

• Delay in source control > 24 h

• Inability to achieve adequate drainage/debridement

RISK FACTORS ASSOCIATED WITH ABX RESISTANCE:

• Healthcare acquired infection

• Travel to areas with high resistance rates within a

few weeks prior to getting ill

• Known colonization with MDR

ENTEROCOCCUS: likely only pathogenic (and therefore coverage is necessary) in:

• Health-care associated infxn

• Distal colon surgery

• Hepatobiliary/pancreatic infxn

• Chronic illness

• Immunocompromised

• Valvular disease

• Prosthetic heart valve

• Previous txt with cephalosporins

• Enterococcus is predominant organism on culture

CANDIDA: only treat when yeast/candida on gram stain/culture AND one of the following:

• Yeast seen intracellularly

• Presence of hyphae

• Immunocompromised

• Multiple previous antibiotics

• Upper GI perforation

• Post-operative IA infection

• Recurrent IA infection

► If C. albicans: add fluconazole (or micafungin if fluconazole-resistnat)

► If non-albicans: add echinocandin

TREATMENT GOALS:

• Control bacteremia & prevent metastatic foci

(gram negative)

• Reduce suppurative complications (anaerobes)

• Prevent local spread of existing infection

o Surgery + antibiotics

• Prevent morbidity and mortality

CLINICAL PRESENTATION:

General Look “toxic”, acute distress, lying still, dehydrated

CNS Febrile, may increase rapidly; ↓ LOC if “septic”

HEENT Grimacing, diaphoretic, dry mucous membranes

RESP ↑ RR, rapid, shallow breathing

CVS ↓BP, ↑ HR, may require fluid/vasopressors for septic shock

GI/GU Bowel sounds initially faint, may disappear; voluntary guarding; abdominal pain/tenderness; N/V

ABD X-RAY Bowel distension, “free air” = perforation surgical emergency

LABS ↓ urine output, ↑ BUN, ↑ SCr, ↑Hb/Hct, alkalosis then acidosis

MSK/DERM ↓ skin turgor, cool, clammy extremities

Page 3: Lecture 24 Intra-abdominal Infections Lalji INTRA ... · • Cholangitis and cholecytitis ... • Relatively uncommon, but most commonly in pts with chronic liver disease o SBP occurs

Lecture 24 Intra-abdominal Infections Lalji

PERITONITIS (CONTINUED):

SECONDARY PERITONITIS:

TREATMENT FOR COMMUNITY-ACQUIRED:

• No consensus on drugs of choice for empiric coverage – studies show similar cure rates if gram (-) and anaerobic coverage is included

• Antibiotic selection should always encompass host, bug and drug factors

Type Definition Single agent regimens Combination regimens Notes

Low-risk community-acquired

Mild-mod severity (including perforated appendix or appendiceal abscess) in absence of risk factors for failure of resistance

• Ertapenem

• Pip/Tazo

• Cefoxitin, moxifloxacin, clindamycin, tigecycline o Acquiring more

resistance so generally avoid

o Tigecycline = increased mortality

Cefazolin, cefuroxime, ceftriaxone, cefotaxime, ciprofloxacin, levofloxacin PLUS metronidazole

If need enterococcoal coverage, use:

Ampicillin 2 g IV q6h

PLUS

Gentamicin 5-7 mg/kg IV q24h

PLUS

Metronidazole 500 mg IV/PO BID

High-risk community-acquired

Severe infections or in patients at high risk for adverse outcomes or resistance

• Imipenem, meropenem, doripenem

• Pip/tazo

Cefepime, ceftazidime, ciprofloxacin, levofloxacin PLUS metronidazole

If need enterococcal coverage, use

Pip/Tazo PLUS gentamicin

TREATMENT FOR HEALTHCARE ASSOCIATED:

• High risk of resistant pathogens and therefore need coverage for streptococci (incl. enterococci), anaerobes (incl. B. frag) and resistant

enterobacteriaceae and P. aeruginosa

Carbapenem Pip/tazo Ceftazidime or cefepime WITH metronidazole

Aminoglycosides Vancomycin

If < 20% resistance with P. aeruginosa, Acinetobacter, or multi-drug resistant gram (-) bacilli (MDR GNB)

✔ ✔ ✔ ✔ ✖

ESBL-producing Enterobacteriaceae ✔ ✔ ✖ ✔ ✖

MRSA ✖ ✖ ✖ ✖ ✔

STEPDOWN:

• Continue IV abx until patient clinically well, including tolerate oral medications, afebrile, WBC normal, no residual fluid collections, return of GI fxn

• Oral step down:

• Amox/clav 875 mg PO BID

• 3rd/4th gen cephalosporin + metronidazole 500 mg PO BID

• TMP/SMX 1 DS BID + metronidazole 500 mg PO BID

• Ciprofloxacin 500 mg PO BID + metronidazole 500 mg PO BID o Can substitute levo/moxifloxacin

• Total duration is around 4-7 days

INTRA-ABDOMINAL ABSCESS:

• Purulent collection of fluid surrounded by a wall

(fibrinous capsule) from the surrounding tissue

• May range from a few mL to a L in volume

• Located in peritoneal cavity of within visceral organs

• Takes days to years to form

• Commonly seen in appendicitis, diverticulitis,

pancreatitis, female GU tract

• Ultrasound or CT scan may be used for evaluation

• Often need to drain abscess

• Need anaerobic coverage

ACUTE APPENDICITIS:

• Characterized by acute onset of N/V, RLQ pain, rebound tenderness, low-grade fever, anorexia

• Surgery, rather than antibiotics alone, remains gold standard (↑ recurrence with abx alone)

o Either open or laparoscopic surgery

▪ Laparoscopic surgery = fewer wound infections, less pain, shorter hospital

stay BUT higher rates of re-admission and abscess

o Antibiotics given pre-op and sometimes up to 24-hr post-op (ex// cefazolin 1-2 g)

• In patients with over 5 days of symptoms, a cooling-off approach may be used with hydration,

antibiotics, bowel rest and elective appendectomy 6-8 weeks later

• If appendix is perforated or gangrenous, or abscess seen, then treatment is surgery and

antibiotics as per mild-moderate secondary peritonitis (duration is ~ 3 days)

TREATMENT PRINCIPLES:

• Surgical: drainage of abscess/debridement; resection of perforated abdomen (colon, small intestine, ulcers); repair of trauma

• Support of vital functions: monitor BP, heart rate, urine output (0.5 mL/kg/hr)

• Antimicrobial therapy: empiric regimens should minimally cover E. coli, Klebsiella spp., Bacteriodes fragilis, Clostridium spp.

Page 4: Lecture 24 Intra-abdominal Infections Lalji INTRA ... · • Cholangitis and cholecytitis ... • Relatively uncommon, but most commonly in pts with chronic liver disease o SBP occurs

Lecture 24 Intra-abdominal Infections Lalji

ACUTE CHOLECYSTITIS AND CHOLANGITIS: inflammation of the gallbladder and ducts

CAUSES:

Gallstones • Most cholecystitis is the result of hard particles that develop in your gallbladder (= gallstones) from imbalances in the substances in bile (ex// cholesterol and bile salts)

• Gallstones can black the cystic duct (tube through which bile flows through when it leaves the gallbladder) causes bile to build up inflammation

Tumor • A tumor may prevent bile from draining out of your gallbladder properly bile buildup cholecystitis

Bile duct blockage

• Kinging or scarring of bile ducts can cause blockage that leads to cholecystitis

COMMON SYMPTOMS:

• RUQ pain

• Fever

• Leukocytosis

• Jaundice

• If severe, mental status changes and sepsis

MAIN PATHOGENS:

• Enterobacteriaceae, enterococcus, anaerobes

PATHOPHYSIOLOGY:

• A biliary system that is colonized by bacteria (it’s normally stable)

but is unobstructed typically doesn’t result in cholangitis

• Biliary obstruction diminishes host antibacterial defenses, causes

immune dysfunction, and subsequently increases small bowel

bacterial colonization

o Bacteria gain access to the biliary tree by retrograde ascent

from the duodenum or from portal venous blood

o Infection ascends into hepatic ducts, causing serious infxn

o Increased biliary pressure pushes infection into biliary

canaliculi, hepatic veins, and perihepatic lymphatics

bacteremia (25-45%)

o The infection can be suppurative in the biliary tract

TREATMENT:

• Initial supportive care with hydration, pain control & bowel rest

• Same as treatment of appendicitis: surgery > antibiotics alone

o Antibiotics given pre-op and sometimes up to 24-hr post-op

(ex// cefazolin 1-2 g)

• If gallbladder is perforated or gangrenous, or abscess seen, then

treatment is surgery and antibiotics as per secondary peritonitis

(short-course: 3-5 days)

DIAGNOSIS:

• DDx: ultrasound and CT scan

• Consult: GI and surgery