ID Pharmacotherapy - 04/20 2a IAIs

What is the function of

stomach,

pancreas,

gallbladder,

common bile duct,

SI,

LI

Appendix?

• Stomach: store food and secrete acid

• Pancreas: secrete enzymes to digest fats, carbs, proteins, glucagon, and insulin

• Gallbladder: hold bile from liver for fat and food digestion

• Common bile duct: connect to duodenum

• SI: DJI that absorbs nutrients

• LI: water absorption and feces storage

• Appendix: attach to colon, vestigial

What is the peritoneal space?

• Under diaphragm to pelvic floor

• Holds stomach, SI, LI, liver, gallbladder, spleen, 100ml of sterile fluid

• Linked w/ peritoneum that is highly permeable and heavily innervated w/ nerve endings

What is the retroperitoneal space?

Holds duodenum, pancreas, kidneys, adrenals

What are IAIs and what are the common ones?

• Heterogenous infection groups w/in abdominal space involving peritoneal or retroperitoneal space

• Appendix: Appendicitis

• Gall bladder: Cholecystitis

• Common bile ducts: Cholangitis

• Colon: colitis

• Diverticulum of colon: Diverticulitis

• Pancreas: pancreatitis

How are IAIs classified?

CA vs HA

Uncomplicated vs complicated

What is CA vs HA IAI?

Community acquired

No relevant HC exposure

Narrow pathogen spectrum

Low resistance likelihood

HC acquired

Relevant HC exposure

Broad pathogen spectrum

Increased resistance likelihood

What is uncomplicated vs complicated IAI?

Uncomplicated

Restricted to source organ

Complicated (harder to treat and more severe)

Infections extends past source to:

Peritoneal cavity,

Retroperitoneal space

Another ab organ

Ab wall

or is associated w/ peritonitis or abscess formation

What is peritonitis?

Acute inflammation of peritoneal lining due to contamination by microbes, chemicals, foreign-body injury

What are the types of peritonitis?

Primary AKA spont bacterial: no clear contamination source and occurs in ascites and liver cirrhosis

2ndary: clear contamination source and seen in GI perf, ab surgery/trauma

Tertiary: infection persists or recurs after 48hrs of appropriate management of 2ndary peritonitis (less well defined)

What is an IAI abscess and its importance?

Purulent collection of fluid w/ tissue debris, bacteria, inflammatory cells surrounded by fibrinous capsule

Volume can vary

Abx cannot penetrate well, need to drain and source control

What is the pathophysiology of uncomplicated IAIs?

Obstruction in lumen of organ/duct leads to stasis

Stasis leads to microbial overgrowth

Overgrowth leads to inflammation

Seen in cholecystitis, cholangitis, appendicitis

What is the pathophysiology of peritonitis?

Microbiology entry into peritoneal or retroperitoneal space

Host immune response cannot contain microbes leading to dissemination throughout cavity and peritonitis and increased permeability (cytokine effs)

Allows fluids, proteins, etc. in to cause 3rd spacing, hypovolemic shock

Allows bacterial endotoxins into blood to cause septic shock

What is the pathophysiology of IAI abscess?

Microbiology entry into peritoneal or retroperitoneal space

Host immune response CAN contain microbes but not eliminate

Leads to tissue necrosis, local thrombosis, extension into surrounding tissues

Fibrin capsule produced to shield hold from bacteria and tissue debris

What is the basic microbiology of IAI?

Usually polymicrobial and caused by GI flora:

Strep

Enteric gram- (esp E coli)

Anaerobes (esp Bacteroides)

Enterococci (may be bystander)

MORE POSSIBLE PATHOGENS AND RESISTANCE IF HA-IAI

What are possible pathogens in CA-IAI?

Enteric gram-: E coli, Klebsiella, Enterobacter, Proteus

Some gram+: strep

Anaerobes: Bacteroides, Clostridium

What are possible pathogens in HA-IAI?

Enteric gram-: E coli, Klebsiella, Enterobacter, Proteus, Pseudomonas, Acinetobacter

Some gram+: strep, coag- staph, staph aureus, enterococcus

Anaerobes: Bacteroides, Clostridium

Fungi candida

What is the clinical presentation of IAI?

Wide spectrum depending on disease process, location, magnitude of contamination, host factors

Usually localized or diffuse Ab bain

GI dysfunction

Nonspecific inflammation signs

What are the localized abdominal pains point to depending on the quadrants?

LUQ: diverticulitis, splenic abscess

RUQ: diverticulitis, cholecystitis, cholangitis, pancreatitis, hepatic abscess

LLQ: diverticulitis, PID

RLQ: appendicitis

What are the signs that are seen w/ diffuse ab pain of IAI?

Usually in 2ndary or tertiary peritonitis

Rigid ab

Sepsis

3rd spacing

Hypovolemia or sepsis

More severely ill

How is IAI diagnosed?

Symptom Hx + physical exam + Radiographic

Ultrasound

CT of ab + pelvis using oral radiocontrast dye (GOLD STANDARD):

Free air = intestinal perf

Air-fluid levels = abscess

Diagnostic laparoscopy if needed

What is the IAI management approach?

Fluid resuscitation and maintenance of organ function

Source control

Empiric Abx

Targeted Abx based on susceptibilities

D/C if endpoints met

What is source control in IAI?

Procedure performed to:

Eliminate source of infection,

Control ongoing contamination, or

Correct anatomic derangements and restore normal function/anatomy

What is the goal of source control in IAI and why is it important?

Reduce microbial burden and toxin load so immune system + Abx can eradicate infection

Most treatment failure b/c inadequate source control

What are the types of source control?

Percutaneous abscess drainage

Laparoscopy: less invasive method used in uncomplicated appendicitis and cholecystitis for organ removal

Laparotomy: open surgery for complex, diffuse, complicated infections

What are the goals of IAI Abx therapy?

Control bacteremia or prevent metastatic focus of infection

Prevent local spread of existing infection

Reduce abscess formation risk

Appropriately use Abx and reduce resistance risk

What are the Abx that aren't usually used for empiric IAI treatment and why?

DONT USE IF >10 to 20% RESISTANCE ON ANTIBIOGRAM

Ampi/sulb or augmentin: E coli resistance

FQs: only use if <10% local resistance in E coli

Moxi: avoid if FQ used w/in 90d b/c B fragilis resistance

Cefotetan or clinda: B fragilis resistance

What does the selection of IAI empiric therapy depend on?

Significant HC exposure

RFs for treatment failure or death

If sig HC exposure: use HA-IAI empiric Abx

If not sig HC exposure + high risk for failure/death: use high-risk CA-IAI empiric Abx (same as HC)

If not sig HC exposure + low risk for failure/death: use low-risk CA-IAI empiric Abx

What are the characteristics of significant HC exposure that are used in decision making for empiric treatment of IAI?

Infection >48hrs after initial source control

Post-op infection

Hosp <38hrs during current hosp admission

Hosp >48hrs w/in 90d

Live in SNF or LTC facility w/in 30d

Home infusion, wound care, or dialysis w/in 30d

At least 5d of broad spectrum Abx w/in 90d

Known to be colonized or previously infected w/ resistant pathoge

What are the RFs for treatment failure or death that are used in decision making for empiric treatment of CA-IAI?

Delay in initial source control >24hrs

Inability to achieve adequate source control

Severe disease (APACHE >15)

Diffuse, generalized peritonitis

>70yos

Comorbidities and degree of organ dysfunction:

sig CV compromised

Sig liver disease

Sig renal disease

Poor nutrition/hypoalbuminemia

Immunocompromised:

Meds, HIV, malignancy, transplant

Prolonged LoS before op (>5d) and prolonged preop Abx (>2d)

What is the empiric treatment of low-risk CA-IAI?

Monotherapy: ertapenem, moxi

Combo therapy

Cefazolin, cefuroxime, ceftriaxone, cefotaxime, cipro, or levo + METRONIDAZOLE

Avoid FQs if used w/in 90d or E coli resistance>10%

What is the empiric treatment of high-risk CA-IAI?

SAME AS HA-IAI

Monotherapy: imipenem/cilastatin, meropenem, doripenem, pip/tazo

Combo therapy

Cefepime, ceftazidime, or aztreonam + METRONIDAZOLE

If using aztreonam: add vanc to cover strep

If using cefepime, ceftazidime: consider ampi or vanc to cover E faecalis

What is the empiric treatment of HA-IAI?

SAME AS HIGH-RISK CA-IAI

Monotherapy: imipenem/cilastatin, meropenem, doripenem, or pip/tazo

Combo therapy

Cefepime, ceftazidime, or aztreonam + METRONIDAZOLE

If using aztreonam: add vanc to cover strep

If using cefepime, ceftazidime: consider ampi or vanc to cover E faecalis

What are the special organisms to consider in IAI empiric treatment?

ESBL enterobacteriales

MRSA

VRE

Candida

Only cover if organism-specific RFs present

When is empiric MRSA coverage in IAI warranted and what is used?

NOT CA-IAI

HA-IAI if known to be colonized OR previous treatment failure + sig Abx exposure

Vanc

When is empiric enterococcus (non-VRE) coverage in IAI warranted and what is used?

NOT LOW-RISK CA-IAI

High-risk CA-IAI + HA-IAI if

immunocompromised,

post-op peritonitis,

severe sepsis from abdomen after receiving cephalosporins, OR

Peritonitis w/ heart valve disease or prosthetic material

Pip/tazo

Imipenem/cilastatin

Meropenem (some resistance)

Add ampi to normal regimen

Add vanc to normal regimen

When is empiric VRE coverage in IAI warranted and what is used?

Known to be colonized

Liver transplant recipient w/ infection originating in hepatobiliary tree

Add linezolid to normal regimen

Add daptomycin to normal regimen

When is empiric candida coverage in IAI warranted and what is used?

Not in low-risk CA-IAI

Critically ill + high-risk CA or HA + one of following:

Upper GI source of infection

Recurrent bowel purf

Surgically treated pancreatitis

Prolonged broad Abx but still doing poorly

Heavy candida colonization

Echinocandins: caspofungin, anidulafungin, micafungin

Can use fluconazole if shown sensitive (NOT EMPIRIC)

Why does the duration of IAI therapy matter?

Reduce Abx resistance

Reduce ADrs

Reduce CDI

What is the duration of most IAIs and what is it based off of?

4 to 7d if adequate source control

Longer if inadequate source control

Depends on defervescence, normalization of WBCs, PO tolerance

In certain scenarios, only need 24hrs of Abx

What are the scenarios in which <24hrs of Abx are required for IAI treatment?

Traumatic or iatrogenic bowel injury operated on w/in 12hrs

Upper GI perf operated on w/in 24hrs w/o acid suppressive therapy or malignancy

Non-perf appendicitis w/ appendectomy

Non-perf cholecystitis w/ cholecystectomy