Download - 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


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%


• 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


• 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


• 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


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)


• 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.


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