PHAR 506: Exam II Lecture Review

(2/14) Gross Lecture: Intraabdominal Infections Intra-abdominal Infections (IAI): IAI is a general category for a broad constellation of infections varied by severity and exposure. Included are: Peritonitis, Abscesses, Complicated IAI, Cholecystitis/Cholangitis, and Appendicitis Quick Microbial Group definitions

- “Enterics”: Also known as Enterobacteriaceae: E. coli, Klebsiella pneumoniae, - IAI-related Anaerobes: Bacteroides, Clostridium, peptostreptococcus - Enterococcus: Aerobic gut bacteria

Inhabitants of the Peritoneal Cavity Normal flora and their anatomical homes - Stomach: Steptococcus, Lactobacillus - Biliary Tract: Enterics, Enterococcus, though usually sterile. No anaerobes. - Proximal SI: Streptococcus, Enterococcus, Enterics, Lactobacillus, Diphtheroids - Distal SI: Enterics, Enterococcus, Bacteroides f, Clostridium, peptostreptococcus - Colon: Bacteroides, Peptostreptococcus, clostridium, enterics, candida - Stool: 50% of stool weight is Bacteroides bacteria. - Significant Absence: Note, Pseudomonas and Staph aureus are generally not present.

o Healthcare-associated diagnoses have a higher incidence of pseudomonas, due to GI surgery Treatment Spectrum by Bug-type

- These are generalizations, consult your local Antibiogram. Typically, we want 80% activity minimum. Higher percentages are based on the risk/benefit of therapy and the severity of the infection

Enterobacteriaceae GI Anaerobes Pseudomonas Enterococcus faecalis Enterococcus faecium à Ceftriaxone à Pip/Tazo (Zosyn) à Cefepime

à Pip/Tazo (Zosyn) à Carbapenems à Metronidazole (Flagyl)

à Pip/Tazo (Zosyn) à Carbapenems* à Cefepime

à Ampicillin/Sulbactam (Unasyn) à Pip/Tazo (Zosyn) à Imipenem, Vanco, Linezolid, Daptomycin

à Linezolid à Daptomycin

Problems: fluoroquinolones +cillins have poor susceptibility

Success Story: Flagyl is active for essentially all anaerobes, susceptibility is rarely tested. Problems: Clindamycin has hella resistance. Not used.

Problems: Ertapenem is a carbapenem with NO coverage

Problems: Try not to confuse with faecium

Problems: Essentially all enterococcus faecium are VRE

- Arsenal of Reserves: Ceftazidime/Avibactam, Ceftolozane/tazo, meropenem/vaborbactam, and Tigecycline are all agents we can use as well, however are reserved due to their broad-spectrum activity or risk of toxicity.

- Tigecycline: Kills patients. High risk of mortality, the FDA has a BBW. We only use it as a last resort. Dx: Peritonitis

- Patho: This simple IAI is an inflammatory response of the peritoneum secondary to bacterial infection. It can be primary/spontaneous, secondary (CIAI), or tertiary.

- Peritoneal Dialysis-associated: Offers many infectious agents passage into the cavity via equipment o Likely cause: Skin flora (think Staph aureus, staph epidermis)

Primary Peritonitis ~ Spontaneous Bacterial Peritonitis (SBP): SBP most frequently affects cirrhotic patients or patients otherwise experiencing liver failure.

- Etiology: Primary = no specific source, we have no clue where it came from o Usual cause is the translocation of bacteria to the peritoneal space due to a state of increased intestinal

permeability. May also be hematogenous (from the blood), or from the lymphatics o PPI use can decrease our normal ability to clear bacteria from the GI tract, causing a change in flora

- Sx: Fever, Abdominal distention/pain, worsening/altered mental status (enceph), N/V, Hypovolemic hypotension due to fluid shifts.

- Dx: Requires (1) SBP Syndrome, (2) and + Paracentesis results of the ascites fluid o PMN (Neutrophils) > 250/mm3, Gram stain results (Protein < 1g/dL suggests primary) o Likely Bacterial Cause: Monomicrobial. Streptococcus, Enterics o Unlikely Cause: We can assume there are no anaerobes and no Staph aureus – yay!

n Tx: Ceftriaxone or Cefotaxime for 5 days. Noticeable improvement in 24-48h, otherwise repeat paracentesis o These drugs are indicated for gram(+) and enterics (gram(-) bacil). They are the narrowest spectrum we

have. They do not cover for staph or anaerobes, which is ok o Future Prophaylaxis: Fluoroquinolones or Sulfamethoxazole/Trimethoprim (Bactrim)

Abscesses: A focal collection of necrotic tissue, bacteria, and inflammatory cells (WBC). Often preceded by peritonitis, it is the walled-off pool of dead shit

- Sx: Non-specific - Dx: Imaging tools are the primary method for diagnosis. Such as a CT or Ultrasound

o Likely Bacterial Cause: Often Polymicrobial. Causative microbe depends on origin and risk factors - Tx: Most importantly, proper treatment requires Source Control. Abscesses may be full of infectious agents and

may be leaking. Improper drainage may prolong therapy for weeks. o (1) Drain the Abscess using a percutaneous catheter or surgery. (don’t forget to culture what comes out!) o (2) Antibiotic therapy based off likely bacterial cause.

Complicated Intraabdominal Infection (CIAI): A Complicated IAI involves anatomical disruption that allows an infection to extend beyond a single organ. Simply put, it affects more than 1 site. This infection is most frequently found in patients who are critically ill, protein-shifted, fluid-shifted, in organ failure, or experiencing abdominal distention.

- Risk Factors: Critically ill in the ICU, trauma, surgery complications - Sx: Abdominal Symptoms, Fever, Fatigue - Dx: Imaging tools, patient history, and paracentesis (protein > 1g/dL suggests secondary peritonitis à CIAI)

o Mild/Moderate Community-Acquired o High-Risk/Severe Community Acquired: Often the ICU patients in advanced aged. Patients with organ

dysfunction, comorbidities, and poor nutritional status, potentially exhibiting a high severity of illness. This may include immunocompromised patients or individuals who were unable have drainage controlled

o Healthcare-associated: Presence of an invasive device, surgery (think Pseudomonas), History of MRSA, history of residence in a long-term care facility in past 12mo, dialysis, or onset >48h post-admission

o Likely Bacterial Cause: Often Polymicrobial, including Enterics and Anaerobes. If High-Risk Community-Acquired or Healthcare-associated,

§ Additional coverage for Pseudomonas § Additional coverage for Enterococcus (non-VRE)

n Tx: Mild/Moderate Community-Acquired o Metronidazole + Ceftriaxone. Switching Ceftr to fluoroquinolones is preferred if we know it’s active.

Other options include Cefoxitin, Moxifloxacin, & ertapenem. n Tx: High-Risk/Severity Community-Acquired AND Healthcare-Associated

o Pip/Tazo or Imipenem/cilastatin or meropenem or doripenem § Though, the carbapenems are overly broad and less favored

o Type-1 b-lactam allergy: à Vanco (strep coverage) + Metronidazole (Anaerobe Coverage) Cholecystitis/Cholangitis: Cholecystitis refers to inflammation or infection of the gallbladder, whereas cholangitis relates to the bile ducts. This often occurs as a result of obstruction of the normal bile flow due to gallstones, or more rarely acalculous, such as tumors or strictures.

- Sx: Right upper-quadrant abdominal pain that is continuous. Fever, tachycardia, Jaundice o Labs: Leukocytosis, elevated bilirubin, alkaline phosphataseÝ

- Dx: Ultrasound is typically the first diagnostic instrument, used to image the area. o Murphy’s sign (cholecystitis only): Palpate over the gallbladder, have them exhale, then they won’t

inhale because it will be too painful o Likely Bacterial Cause: Enterics, Enterococcus. Anaerobes are unlikely, unless pt hx of biliary-enteric

anastomosis. - Tx: Source Control comes first: Depending on the nature and cause of infection, the gall bladder may need to be

removed. If there is stricture in the biliary tree, an endoscopic retrograde cholangiopancreatography (ERCP) may be performed to break up the blockage, and put a stint in.

n Tx: Mild/Moderate Community-Acquired o Ceftriaxone is sufficient

n Tx: High-Risk/Severity Community-Acquired AND Healthcare-Associated AND Cholangitis Anastamosis o Pip/Tazo + Antipseudomonal Carbapenem. The additional anaerobic and pseudomonas coverage is

preferred in these patients. Appendicitis: Most common in younger patients, appendicitis is an acute inflammation of the appendix related to obstruction. There is a 7.5% lifetime risk

- Sx: Deep periumbilical pain that migrates to the lower right quadrant after 6-24h. o Labs: Mild leukocytosis, elevated CRP

- Dx: Imaging via Ultrasound, CT, or MRI. Dx by exclusion, rule out uterine/ectopic pregnancy in women of childbearing potential

o Likely Bacterial Cause: Polymicrobial, aerobic and anaerobic enteric gram(-), streptococci. - Complications: Appendicitis may lead to perforation, peritonitis, or development of abscesses. A high fever or

sudden decrease in pain may suggest perforation. Additionally, abdominal rigidity/guarding may suggest peritonitis.

- Decision to Treat: Source control via appendectomy has historically been curative and offered as the standard of care. However more recently, we have found in uncomplicated cases antibiotic therapy without surgery may be sufficient.

n Tx: Mild/Moderate Community-Acquired o Metronidazole + Ceftriaxone. Switching Ceftr to fluoroquinolones is preferred if we know it’s active.

Other options include Cefoxitin, Moxifloxacin, & ertapenem. n Tx: High-Risk/Severity Community-Acquired AND Healthcare-Associated

o Pip/Tazo or Imipenem/cilastatin or meropenem or doripenem § Carbapenems are overly broad and less favored

o Type-1 b-lactam allergy: à Vanco (strep coverage) + Metronidazole (Anaerobe Coverage) Special Cases of Empiric Therapy for Anticipated Resistance

- Vancomycin – Anticipating MRSA (Methicillin-Resistant Staph Aureus) o Vanco may be added to the regimen for healthcare-associated CIAI for previously failed treatment and

significant antibiotic exposure - Daptomycin/Linezolid – Anticipating VRE (Vancomycin-Resistant Enterococcus)

o Empiric tx with these abx may be added for patients who have a hx of liver transplant and are infected with IAI originating from the hepatobiliary tree…. Or if straight-up known to be colonized with VRE.

Interpreting Culture Data - Use it. - De-escalation – Based on culture results, de-escalate therapy to more narrow therapies. The only cases where

greater caution should be taken includes location sites or events in which anaerobes would be expected. Anaerobes often do not grow when cultured, so if they’re expected, we cannot discount them.

- Escalation – Based on culture results, escalate therapy to target the isolated resistant pathogen if the infection persists. In the case where Candida is isolated, we will need to initiate anti-fungal therapy

Duration of Treatment Argument - The IDSA and SIS generally have the same suggested protocols for the management and treatment of infections.

However, in 2015 a trial studying the efficacy of short-course anti-microbial therapy for IAI found: o à Following Source Control, 4 days of antibiotic therapy is sufficient o Previously, it was suggested to continue therapy 2 days AFTER normalization of fever/WBC/able to eat. o The results of the study showed equivalence, which is why the shorter therapy is therefore favored.