Download A4 IAI - Pharm D Notes

Intra-abdominal Infections (IAI)
Objectives - 3
1. Discuss the classification, microbiology, and approaches to therapy for iAI.
2. Recommend appropriate, evidence-based antimicrobial treatment regimens for IAI.
3. Describe the role of a pharmacist in antibiotic stewardship for IAI.
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Classification - 5
Intra-abdominal infections occur when there is
growth of microorganisms in normally sterile
regions of the abdomen specifically the
peritoneal cavity or the retroperitoneum.
IAI can be classified as either uncomplicated or
complicated infections
• Uncomplicated infections – are those that
are contained within the wall of an
abdominal organ
• Complicated infections – extends out
beyond the hollow viscous of origin, and they
consist primarily of either peritonitis (reaction of inflammation within the peritoneum) or the
formation of an abscess (natural progression of peritonitis).
The terms uncomplicated versus complicated is not meant to refer to the severity of infection
Peritonitis can also be classified further into primary, secondary, or tertiary.
Primary peritonitis occurs when there is no evident abdominal source or any sort of breakdown in the
integrity of the gastrointestinal tract.
• Primary peritonitis is typically monomicrobial infection.
• The most common form of primary peritonitis is Spontaneous Bacterial Peritonitis (SBP)
• Usually seen see in patients who are cirrhotic or nephrotic
• These infections are caused by enteric gram-negative bacilli
• Peritonitis that occurs secondary to peritoneal dialysis (due to indwelling peritoneal dialysis catheter) is
also considered a form of primary peritonitis (Skin flora like staphylococci)
Secondary peritonitis occurs when there is a perforation / breakdown of the gastrointestinal tract
• In contrast to primary peritonitis these are polymicrobial infections.
• A common example of secondary peritonitis would be a perforated appendicitis.
Tertiary peritonitis is a vaguely defined entity, but can be described as persistent or recurrent infection
that occurs after failure of initial therapy for secondary peritonitis.
• It is also polymicrobial in nature
• Some “experts” would describe tertiary peritonitis as being secondary peritonitis caused by
Pseudomonas, MRSA, Vancomycin Resistant Enterococcus (VRE), or Candida species.
Microflora of the GI Tract - 7
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In order to understand the microbiology of intra-abdominal infections it is important to first understand
the normal flora of the gastrointestinal tract.
The type and number of bacteria differs by the location within the GI tract.
Moving from the top to the bottom of the GI Tract there is an increasing number of bacteria.
• There is very little bacteria found in the stomach due to the acidic environment
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Moving down to the distal ileum or the colon large amounts of pathogens / bacteria are present with
anaerobes being predominant.
Microbiology of Intra-abdominal infections (IAI) - 8
The pathogens associated with IAI are those that are a part of the normal flora.
IAI are polymicrobial infections
The primary anaerobic pathogen we are concerned about is Bacteroides fragilis
Fungal infections of the peritoneum and retroperitoneal space due to Candida species are also implicated
in the microbiology of IAI.
★ The microbiology of intra-abdominal infections differ significantly in patients who have Community
Acquired infections versus Healthcare Associated Infections
• Community Acquired incidents – E. Coli,
Streptococci, Bacteroides comprise a large
portion
Gram-negative bacilli Gram-positive cocci
• Healthcare Associated – common bacteria are still
implicated, but a shift to other gram-negative
Escherichia coli
Streptococci
bacteria such as Enterobacter, Pseudomonas,
Klebsiella species
Enterococci
Staph. Aureus, and Enterococci (existing within
Proteus species
Staphylococci
the hospital)
Pseudomonas
Enterobacter species
Healthcare-Associated Infection - 10
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These patients are at an increased risk of infection
with multidrug resistant organisms
The definition in the IDSA guidelines to define
Healthcare Associated Infections include:
Anaerobes
Bacteroides fragilis
Other Bacteroides spp.
Clostridium species
Fungi
Candida Species
Community-onset
• Presence of invasive device (catheters) at
admission
• A history of MRSA infection or colonization
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Surgery, hospitalization, dialysis, immunocompromised or long-term care facility resident in the
previous 12 months
Hospital-onset
• Associated with a positive culture results obtained ≥ 48 hours after their hospital admission
★ Stratifying between community-onset and hospital onset will have important implications on how the
patients are treated empirically.
Clinical Presentation - 11
Signs and symptoms of IAI correspond with severity of illness and include:
• Abdominal pain, nausea, vomiting, fever
• Tachycardia, tachypnea, hypotension, and decreased urine output
• Typically found in patients that are more critically ill. (e.g., septic shock)
• Upon Physical examination these patients may have:
• Guarding, Abdominal tenderness and distention, and Pain upon palpitation.
Diagnostics - 12
Radiographic
• CT scans, are preferred
• Ultrasonography are less sensitive and specific.
Microbiological
• Community-Acquired Infections the gram stain is of little value, and routine culturing is optional
• Considered in communities with high rates of resistance for common pathogens such as E. Coli.
• Intraoperative cultures are recommended for:
• Healthcare-Associated infections, AND high risk Community Acquired infections
• Anaerobes typically do not grow on routine culture media but are present
Approaches to Therapy - 13
1. Fluid resuscitation – Promote physiologic stability, and ensures adequate antimicrobial drug
distribution
2. Surgical intervention – Source control
Antimicrobial therapy – Prompt, empiric administration at the time of confirmed / suspected diagnosis
Source Control “Key to the management of IAI” - 14
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The definition – any interventional procedures used to control or eliminate the focus of an IAI
This may include:
1. Drainage of an abscess or infected fluid collections
2. Debridement of necrotic infected tissue
3. Any other measures to control a source of ongoing microbial contamination and restore normal
anatomy and function within the patient
Failure or inability to achieve adequate source control using these measures has been associated with
very poor clinical outcomes.
Empiric Antimicrobial Therapy - 15
Administering antimicrobial therapy empirically to patients is a balancing act between administering
narrow-spectrum versus broad-spectrum agents. There are pros and cons to both
• Narrow spectrum agents
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Has an increased mortality with the administration of inappropriate therapy
Minimize the potential for development of resistant organisms by “selection pressure” for those
organisms
Broad-spectrum activity
• Ability to “get it right” the first time.
• Avoid the increased mortality associated with inappropriate
therapy
• Increased the toxicity that the patient encounters
• Increasing “selective pressure”
• Increasing the development of resistant organisms
• Increased acquisition cost which are associated with broad-spectrum therapy
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IDSA Guidelines -16
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IDSA previously had 2 different sets of guidelines
by the Surgical Infection Society (SIS) and
Infectious Disease Society of America (IDSA).
Now however they have merged, and there is just
ONE guideline which was updated in 2009
This was endorsed by several key organizations
within the infectious disease community including
the American Society of Microbiology, ASHP,
Pediatric Infectious Disease Society (PIDS), and
the Society of Infectious Disease as Pharmacist
(SIDP)
What is unique about these guidelines is their key
focus on antimicrobial stewardship.
Grading System - 17
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The level of evidence is made up of two components the letter – giving the strength of recommendation,
and the number – assessing the quality of evidence
• Strength of recommendation – Grade A B or C
• Quality of evidence – Level I, II, III
Approach to Antimicrobial Therapy - 16
The guidelines recommend an approach to antimicrobial therapy.
1. Determine the difference between Community acquired IAI versus Healthcare associated IAI
2. If it has been determined to be a community acquired IAI, then determine
3. Whether they are mild - moderate severity or high risk of severity.
Community-acquired IAI - Mild-to-Moderate Severity - 19
1. Activity against common enteric gram-negative bacilli (E. coli, Klebsiella, Proteus and streptococci)
(AI)
2. Anaerobic coverage (Bacteroides fragilis) for distal small bowel, appendiceal, and colon-derived
sources (AI)
3. Narrower spectrum regimens (with no antipseudomonal activity) are preferred (AI)
• Treatment of Enterococcus (AI) and Candida (BII) is not necessary
• Ampicillin/sulbactam not recommended due to high rates of resistance among community acquired E.
coli (BII)
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Clindamycin and cefotetan not recommended due to increasing resistance among Bacteroides fragilis
(BII). Use of cefoxitin debated but listed as single agent option within the guidelines.
Some of the single agent regimens cover more bacteria than is necessary for IAI (e.g Ertapenem &
Tigecycline). ALL lack activity against Pseudomonas
Combination regimens consist of a cephalosporin (cefazolin, cefuroxime, cefotaxime, or ceftriaxone)
PLUS metronidazole. AGAIN no Pseudomonas coverage
• The addition of metronidazole is for the anaerobic activity
Fluoroquinolone-based regimens (Ciprofloxacin or Levofloxacin) PLUS metronidazole is also a
recommended combination regimen
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Risk Factors associated with Poorer Outcomes - 22
ANY patient having ONE of these risk factors is classified as high-risk of severity
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Delay in initial intervention (> 24 hours)
High severity of illness (APACHE II ≥ 15)
Advanced age
Comorbidity, and degree of organ dysfunction
Low albumin level
Poor nutritional status
• Degree of peritoneal involvement or diffuse
peritonitis should be considered in severe category
• Inability to achieve adequate debridement or control
of drainage (Source Control)
• Presence of malignancy (immunosuppressed)
Community-acquired IAI - High Risk of Severity
1. Use broader coverage for gram-negative bacilli (Pseudomonas) (AI)
• Difference between mild/moderate severity versus high risk of severity is coverage for
Pseudomonas
2. Use fluoroquinolones only if > 90% institutional susceptibility to E. coli (BII)
3. Enterococcal activity recommended (BII)
4. Regimens should be adjusted based on culture and sensitivity results (AIII)
• REMEMBER intraoperative cultures should be done with high risk of severity
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Aztreonam (reserved for patients with severe penicillin allergy) or Ceftazidime
• If these regimens are administered there should be the addition of an agent effective against grampositive cocci due to they only gram-negative activity. May add vancomycin
Levofloxacin has better activity against streptococci than ciprofloxacin
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Ceftazidime & cefepime therapy has NO activity against Enterococcal bacteria. The guideline
recommendation is only a (BII) rating giving priority to Pseudomonas coverage.
Healthcare-associated IAI - 25
1. Empiric antimicrobial regimens based on local epidemiology
(AII)
2. Broad-spectrum antimicrobials (BIII)
• Activity against Pseudomonas, enterococci, and B.fragilis
• Addition of an aminoglycoside may be required for adequate gramnegative coverage
3. Regimens should be adjusted based on culture and sensitivity results (BIII)
• Intraoperative cultures recommended in
order to streamline and adjust therapy
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This chart may be used to tailor regimens
for healthcare associated IAI to the
institutions local epidemiology
E.g. If an institution has high rates of
ESBL positive bacteria then considering
Pip/Tazo or Carbapenem would be
appropriate
So Many Agents! How to choose? 27
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Local epidemiology and susceptibility patterns is the primary driver
Patient-specific characteristics
• Allergies, severity of illness, concomitant medications and disease states, recent antimicrobial
exposure
Availability and cost
Formulary restrictions, manufacturer back-orders, acquisition costs (mono versus combination therapy)
Reported Beta-Lactam Allergy - 28
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Extremely important to thoroughly assess what the symptoms of
allergy. Interview patient, if possible
Concerns with alternatives to beta-lactams
• Decreased activity against gram-negative bacilli, gram-positive cocci
• May require additional agents to ensure appropriate antimicrobial coverage
Remember – non-IgE mediated
penicillin hypersensitivity (e.g., rash)
can still safely receive a
cephalosporin or carbapenem
Acute Cholangitis and
Cholecystitis - 29
These are infections involving the
Biliary Tract.
• Enterococcal activity not required
for community acquired infections (BIII)
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• Anaerobic therapy (BII) – Not required for mild-moderate community-acquired infections
However!
• Anaerobic therapy Should be administered to:
• Biliary-enteric anastamosis or biliary instrumentation present (biliary stent)
• Advanced age, severe physiologic disturbance, or immunocompromised state
• Healthcare-associated biliary infection
Anti-Enterococcal Therapy - 30
Who should receive it?
• Directed therapy when enterococci recovered from a HA-IAI (BIII)
• Empiric therapy against E. faecalis for HA-IAI, especially (BII):
• Immunocompromised, Postoperative infection, Valvular heart disease or prosthetic intravascular
implants, Previous receipt of cephalosporins
Tigecycline, Linezolid, and Daptomycin have activity against Vancomycin Resistant Enterococcus (VRE)
Good Activity
Ampicillin/sulbactam
Piperacillin/tazobactam
Imipenem/cilastatin
Vancomycin
Little to no activity
Tigecycline
Linezolid
Daptomycin
Ticarcillin/clavulanate
Aztreonam
Cephalosporins
Meropenem
Doripenem
Fluoroquinolones
Aminoglycosides
Metronidazole
Anti-MRSA Therapy - 32
Who should receive it?
• Empiric coverage should be administered to patients with healthcare-associated IAI (BII):
• Colonized with MRSA or history of MRSA infection
• At risk for infections due to MRSA (e.g., prior treatment failure, significant antimicrobial exposure,
post-surgical IAI)
• Vancomycin is listed in guidelines as 1st line agent for proven or suspected IAI due to MRSA (AIII)
Antifungal Therapy - 33
Who should receive it?
• High-risk community-acquired or healthcare associated IAI when Candida spp. isolated (BII)
• Not recommended in low risk patients, even if fungi recovered
• Preemptive use in high risk patients is not well-defined, but maybe preferred when the bowel is
perforated
For critically ill patients, initial therapy with an echinocandin recommended (BIII)
• Due to the increasing rates of non-albicans Candida spp.
• The Echinocandins are susceptible to most fungal species
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One possible exception could be Candida Parapsilosis, but the rates of resistance are still very low
Duration of Therapy - 35
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Duration of therapy should be limited to 4-7 days, unless unable to achieve adequate source control
• Discontinuance of therapy occurs when afebrile, normalized WBC, or return of GI function
Antimicrobial duration of therapy limited to ≤ 24 hours is appropriate for:
• Intraoperative contamination
• Acute appendicitis without perforation, abscess, or local peritonitis
• Traumatic bowel injuries repaired within 12 hours
Transition to oral therapy acceptable for:
• Patients tolerating an oral diet
• Susceptible to oral agents, if microbiological results available
If a patient has persistent or recurrent clinical evidence of infection after 4-7 days of therapy, a
diagnostic investigation should be performed
Longer durations may be required for patients who who are:
• Immunosuppression, Critically
ill patients, Resistant
organisms, or Inadequate
source control
Patient Case #1 - 38
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DR is a 19 year old male with a
past medical history of allergic
rhinitis who presents to the
emergency department with
constant, sharp RLQ abdominal
pain that has worsened over the
past 12 hours and is now extending the the left side. He also reports chills, nausea, decreased appetite,
and some diarrhea for the past 24 hours.
Physical examination reveals guarding and rebound abdominal tenderness.
His vitals are: BP 110/62 mm Hg, HR 85 bpm, RR 16, temperature 36.8°C
A CT scan is performed which shows acute appendicitis with adjacent peritonitis. DR is scheduled to go
to the OR for laparoscopic appendectomy.
Drug allergies
• Penicillin (rash) occurred after receiving amoxicillin for a dental procedure
Home medications
• Loratadine 10 mg by mouth daily
• Multivitamin 1 tablet by mouth daily
How would this presumed intra-abdominal infection be classified?
• Patient is clinically stable with no exposure to the healthcare system
• No risk factor that would make him a high-risk of severity or poor outcomes
• This patient would be classified as community acquired with mild to moderate severity
What organisms are likely to be playing a role?
• Enteric gram-negative bacilli – E. Coli, or Klebsiella, Proteus
• Gram-positive cocci – Streptococci
• Anaerobes – Bacteroides Fragilis
When should antimicrobial therapy be initiated?
• Immediately
DR is found to have perforated appendicitis with intraoperative evidence of infection.
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What are some options for antimicrobial therapy and should his allergy to penicillin be taken into
consideration?
• Cephalosporin regimens would be appropriate
• An allergy to penicillin would preclude him from Penicillin-based regimens (Ticarcillin)
• Patients reaction to penicillin is “just a rash” which is a non-IgE mediated hypersensitivity reaction
to penicillin.
• This patient can safely receive a cephalosporin (cefazolin, ceftriaxone, in addition with
metronidazole) or a quinolone-based therapy + metronidazole
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Per the resident surgeon, surgical intervention/source control was successful. On POD #2, DR is
without pain, tolerating clear liquid diet, and having bowel movements. They ask for your
recommendation on an oral regimen and length of antimicrobial therapy. What is your response?
• Assuming no other evidence of infection this patient could receive 4-7 days of therapy
• Oral regimen could include: quinolone-based therapy + metronidazole or oral cephalosporin +
metronidazole.
Patient case #2 - 42
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JS is a 35 year-old male s/p liver transplantation secondary to hepatitis C virus 14 days ago. Following
his transplant, he was transferred to the surgical ICU, where he developed respiratory failure and was
subsequently intubated. He received mechanical ventilation (MV) for 5 days and was extubated 9 days
ago. A tracheal aspirate obtained on day 3 of MV grew Enterobacter Cloacae, for which he completed a
7 day course of cefepime. He has NKDA.
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Today, JS develops a new fever, has an elevated WBC count, and complains of diffuse abdominal pain.
A CT scan is performed, which shows an intra-abdominal abscess. Percutaneous drainage of the abscess
is planned.
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How would this intra-abdominal infection be classified?
• This patient has had recent surgery, is immunosuppressed, and would be classified as a healthcare
associated IAI
What organisms are likely to be playing a role?
• Enteric gram-negative bacilli, but ALSO Pseudomonas
• Streptococci
• Post surgery patients are also at risk of MRSA, and also Enterococcus
• Anaerobic bacteria
When should antimicrobial therapy be initiated?
• Immediately
What are some options for antimicrobial therapy?
• We need to provide antibiotics with anti-pseudomonal activity
- Piperacillin/tazobactam, also anti-pseudomonal cephalosporins and carbapenems
• The most appropriate approach is knowing what kind of organisms are typically seen in your
institution, and susceptibility pattern (antibiogram)
• COVER for pseudomonas, anaerobes, MRSA (vancomycin to also cover enterococcus)
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JSs intra-abdominal abscess is successfully drained. A gram-positive organism in pairs and chains and
Candida albicans are isolated from the abscess fluid. Is the Candida albicans significant?
• YES, patient should receive therapy directed at Candida albicans
• Should therapy need to be potentially changed for the gram-positive organism?
• The fact that the bacteria is identified a gram-positive organisms in pairs and chains could lead us to
believe it could be and enterococci or streptococci
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Patient has had recent cephalosporin exposure leading us to assume that vancomycin resistant
enterococcus (VRE). Therapy should cover for VRE
Antimicrobial Stewardship - 45
Potential Roles of a Pharmacist
1. Order sets and clinical pathways development and implementation
2. Antimicrobial restriction - based on formulary or cost
3. Post-prescriptive review
• Optimization of therapy (de-escalation, or may need more potent agents)
• IV to PO conversion
• Optimized duration of therapy
4. Dose optimization
• Pharmacokinetics (vancomycin, aminoglycosides)
• Alternative dosing strategies (prolonged infusions)
5. Tracking epidemiologic patterns within an institution
Summary - 46
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IAI are typically polymicrobial
Antimicrobials with activity against gram negative bacilli, gram-positive cocci, and
anaerobes should be initiated
Spectrum of activity should depend on the patient’s clinical status and risk factors for multidrug resistant
organisms
Source control is crucial
Duration of therapy may be as little as 4-7 days, once source control has been established
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