intra-abdominal%20infections
INTRA-ABDOMINAL INFECTIONS
Intra-abdominal infections (IAI) occur due to disruption of the normal anatomic barrier.
In the hollow viscera is where common disruptions occur, which allows intraluminal bacteria to invade and proliferate in the usually sterile area (ie peritoneal cavity or retroperitoneum).
Community-acquired intra-abdominal infection is usually secondary to gastroduodenal perforation, ascending cholangitis, cholecystitis, appendicitis, colon diverticulitis with or without perforation, or pancreatitis.
Uncomplicated IAI infectious process involves only a single organ and does not extend to the peritoneum.
Complicated IAI is when infection extends beyond the hollow viscus of origin into the peritoneal space and may be associated with peritonitis or abscess formation.

Principles of Therapy

  • Once there is a suspected intra-abdominal infections (IAI), it is proper to begin empiric antimicrobial therapy
    • Initial antibiotic therapy for IAI is always empiric since patient is usually critically ill & that the results of culture & susceptibility take at least 48 hours to become available
    • Antibiotics should be started immediately, w/in 1 hour of recognition of septic shock or w/in 8 hours if w/ no hemodynamic or organ compromise
  • Choice of antimicrobial drugs should be based on the possible organisms involved & risk factors for major resistance patterns, patient’s severity, & identified/suspected source of infection; however, regardless of testing results, antibiotic spectrum must include anaerobic bacteria in community-acquired or nosocomial peritonitis
    • Infections that originated from the stomach, duodenum, biliary system, & proximal small bowel contain Gram-positive & Gram-negative facultative organisms
    • Infections that are from distal small bowel perforations contain Gram-negative facultative & aerobic organisms
      • These perforations typically evolve into localized abscesses & peritonitis develops only after the rupture of the abscess; anaerobes (eg B fragilis) are frequently present
    • Infections derived from the colon may be caused by facultative & obligate anaerobic organisms; Streptococci & Enterococci are commonly present
      • E coli is the most common Gram-negative facultative organism present
  • Antibiotics should be given in patients who will undergo source control procedure to provide surgical wound prophylaxis (given 1 hour before the procedure), treatment of pathogens potentially disseminated during the procedure, & therapy for ongoing infection
  • In patients w/ severe community-acquired (CA)-IAI & hospital-acquired (HA)-IAI, culture & susceptibility results should be used in adjusting the empiric regimen
  • The following are risk factors for multidrug-resistant (MDR)  infection:
    • Broad-spectrum antibiotic treatment failure w/ a 3rd generation cephalosporin, fluoroquinolone, or Piperacillin/tazobactam
    • Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae or Ceftazidime-resistant P aeruginosa isolated on a sample taken in the last 3 months regardless of site
    • Hospitalization in the preceding 12 months in a foreign country
    • Recurrence of infection (<2 weeks) previously treated w/ Piperacillin/tazobactam for 3 days
    • Residence in a long-stay care or nursing home & w/ an indwelling catheter &/or gastrostomy
    • Therapy during the preceding 3 months w/ a 3rd generation cephalosporin or fluoroquinolone

General Principles in Managing Pediatric Patients w/ Intra-abdominal Infections (IAI)

  • For children w/ fever & abdominal pain where complicated appendicitis or other acute IAI is in doubt, routine use of broad-spectrum antibiotics is not recommended
  • Choice of antimicrobial regimen to be used should be based on the origin of infection (CA-IAI vs HA-IAI), severity of the illness, & safety of the drug for each specific age group
    • Consider P aeruginosa in severe cases (eg organ failure or presence of comorbidities, or treatment failure)
  • Broad-spectrum antimicrobial regimens that may be used in pediatric patients include:
    • Aminoglycoside-based regimen (may be an option in children w/ severe reactions to beta-lactams)
    • Carbapenem (Imipenem, Meropenem, Ertapenem)
    • Beta-lactam/beta-lactamase inhibitor combination (Piperacillin/tazobactam, Ticarcillin/clavulanate)
    • Advanced-generation cephalosporin (Cefotaxime, Ceftriaxone, Ceftazidime, Cefepime) + Metronidazole
    • Ciprofloxacin + Metronidazole is recommended for children w/ severe reactions to beta-lactams

Pharmacotherapy

Antimicrobial Therapy
Mild-Moderate Community-acquired Intra-abdominal Infections (CA-IAI)

  • Antibiotics should have a coverage against enteric Gram-negative aerobic & facultative bacilli, & enteric Gram-positive Streptococci
  • Obligate anaerobic bacilli should be covered in infections involving the distal small bowel, appendix & colon, & for proximal gastrointestinal perforations w/ obstruction or paralytic ileus
  • Ampicillin/sulbactam or Cefotetan, Cefoxitin & Clindamycin are not recommended for use because of high resistance rates to E coli & B fragilis, respectively
  • Empiric coverage of Enterococcus & Candida are not necessary in mild-moderate CA-IAI
  • Routine use of aminoglycosides in adults are not advised because of the availability of less toxic drugs

Severe Community-acquired Intra-abdominal Infections (CA-IAI)

  • Quinolones should only be used if hospital survey indicates >90% quinolone susceptibility of E coli
  • Aztreonam + Metronidazole may be an alternative regimen, w/ the addition of a drug effective against Gram-positive cocci
  • Use of agents effective against Enterococci is recommended
  • Agents against Methicillin-resistant S aureus (MRSA) or yeast are not advised unless infection due to such pathogens are present
  • Piperacillin/tazobactam w/ or w/o Gentamicin can be given in critically ill patients
  • Antifungal therapy may be given in patients w/ severe community-acquired or postoperative peritonitis w/ at least 3 of the following criteria: Female, antibiotic therapy >48 hours, hemodynamic failure, or upper gastrointestinal (GI) surgery

Healthcare-associated Intra-abdominal Infections (HA-IAI)

  • Agents to be used should have a wide spectrum of activity against Gram-negative aerobic & facultative bacilli
  • Antifungal therapy in adults is not recommended unless the patient has recently received immunosuppressive therapy for cancer, has gastric perforation & on antacid, has cancer or inflammatory disease, posttransplant, or has a postoperative or recurrent IAI
    • Fluconazole is the treatment of choice if C albicans is isolated
    • For Fluconazole-resistant Candida sp & in critically ill patients, Echinocandin (eg Caspofungin, Micafungin, Anidulafungin) is recommended
      • Echinocandins can also be used in critically ill patients w/ CA-IAI
    • Amphotericin B is not an option for initial therapy due to its toxic effects
  • Anti-enterococcal therapy is recommended especially in patients w/ postoperative infection, have recently received cephalosporins or other antibiotic against Enterococcus sp, immunocompromised, & w/ valvular heart disease or prosthetic intravascular materials
    • Initial empiric antibiotic should be against E faecalis, which includes Ampicillin, Piperacillin/tazobactam, & Vancomycin
    • Agent against Vancomycin-resistant E faecium is not recommended unless patient is a liver-transplant recipient w/ IAI that originates from hepatobiliary tree or the patient is known to be colonized w/ such pathogen
  • Anti-Methicillin-resistant Staphylococcus aureus (MRSA) agents are advised to patients w/ HA-IAI who are known to be colonized w/ the pathogen or to patients w/ prior treatment failure & significant antibiotic exposure
    • Vancomycin is the treatment of choice for treating suspected or proven IAI secondary to MRSA 
  • High risk of MDR bacteria exists in the 1st episode of HA-IAI w/ antibiotic therapy during 3 months prior to hospitalization &/or >2 days before 1st infectious episode &/or an interval of >5 days between the 1st surgery & reoperation

Duration of Therapy

  • Antibiotic treatment can be given for 2-3 days in localized CA-IAI, 5-7 days in generalized CA-IAI, & 5-15 days in postoperative or nosocomial IAI
  • Antimicrobial therapy may be terminated w/ resolution of clinical signs of infection (eg absence of fever, normal white blood cell counts, tolerates oral diet); intensive care unit (ICU) patients w/ multiple organ failure may need computed tomography (CT) scan to know when to stop the therapy (if no defined collections seen)
  • Prophylactic antimicrobial therapy directed against Gram-positive cocci for 24 hours is adequate in patients not on antacid medications w/ acute perforations in the stomach & proximal jejunum or patients w/ cancer, & if source control was done w/in 24 hours; otherwise, antibiotics to cover mixed flora should be given
  • Antibiotics are given for ≤24 hours to patients who had injuries to the bowel secondary to penetrating, blunt, or iatrogenic trauma but are repaired w/in 12 hours & to those who had intraoperative contamination of the operative field
  • Treatment of acute appendicitis w/ no perforation, abscess, or local peritonitis w/ narrow-spectrum regimen active against aerobic, facultative & obligate anaerobes should be discontinued w/in 24 hours

Recommended Empirical Antibiotics for Intra-abdominal Infections (IAI)

Aminoglycoside

  • Very good activity against Gram-negative bacilli but limited Gram-positive cocci coverage
  • Has low penetration in acidic environments, hence not favorable in treating abscesses or IAI
  • Aminoglycosides are associated w/ ototoxicity & nephrotoxicity, & have a narrow therapeutic range
    • Newer non-aminoglycoside agents have been found to be equally effective but w/o the associated toxicities of the aminoglycosides
    • Therefore, these agents should not be considered 1st-line agents & should be reserved for patients that have failed w/ other therapies or have severe allergic reactions to other antimicrobials
  • Aminoglycoside-based regimens are acceptable options for use in pediatric patients w/ IAI & in selected HA-IAI patients depending on local susceptibility patterns
  • May be added to the antibiotic regimen of severely ill patients & to those w/ previous long hospital stay or exposure to antibiotics to increase antibiotic coverage & delay resistance of organisms
  • Gentamicin is part of the regimen option that is commonly used in treating necrotizing enterocolitis in neonates

Anti-anaerobic Agents

  • Metronidazole
    • Given in combination w/ other agents to treat patients w/ CA-IAI, or HA-IAI & necrotizing enterocolitis in neonates
  • Clindamycin
    • B fragilis groups have shown resistance to Clindamycin & therefore, it may no longer be an acceptable anti-anaerobic agent for IAI

Aztreonam

  • When used in combination w/ Metronidazole, may be an alternative to treat severe CA-IAI w/ addition of agents active against Gram-positive cocci

Carbapenems

  • May be used if prevalence of hospital-acquired, extended spectrum beta-lactamase (ESBL)-producing organisms is >20%
  • Ertapenem is appropriate for use in patients w/ mild-moderate CA-IAI as single-agent therapy & acceptable broad-spectrum antibiotic for use in pediatric patients
    • Has activity against ESBL-producing organisms but no activity against Pseudomonas spp & Enterococcus
    • Has a broad spectrum of activity against the commonly isolated Gram-positive cocci & Gram-negative bacilli in IAI
  • Meropenem, Imipenem, Doripenem may be used for severe CA-IAI & HA-IAI
    • Have activity against non-fermentative Gram-negative bacilli
  • Meropenem, Imipenem, or Ertapenem are acceptable options for use in pediatric patients w/ IAI
    • Meropenem is part of the regimen option used in treating necrotizing enterocolitis in neonates
  • Doripenem has broad spectrum in vitro activity against many Gram-positive, Gram-negative, & anaerobic organisms

Cephalosporins

  • Cefoxitin monotherapy is appropriate for use in patients w/ mild-moderate CA-IAI
    • May be used in pediatric patients being evaluated & observed for appendicitis
  • Cefazolin, Cefuroxime, Ceftriaxone & Cefotaxime in combination w/ Metronidazole are appropriate regimens for mild-moderate CA-IAI
    • Ceftriaxone & Cefotaxime in combination w/ Metronidazole may be used in pediatric patients
    • Cefotaxime is part of the regimen option used in treating necrotizing enterocolitis in neonates
  • Cefotetan is no longer recommended for routine empirical therapy since B fragilis have been increasingly found to be resistant to these agents
  • Cefepime & Ceftazidime in combination w/ Metronidazole are recommended for patients w/ high-severity CA-IAI & HA-IAI
    • One of the acceptable broad-spectrum antibiotics used in pediatric patients in combination w/ Metronidazole
  • Consider E coli resistance to 3rd generation cephalosporin if there is >10% local resistance or patient has spent time in areas w/ high prevalence of MDR bacteria

Penicillins w/ Beta-Lactamase Inhibitors

  • Amoxicillin/clavulanic acid is one of the regimens used when shifting to oral therapy, provided that susceptibility results do not show resistance
    • Still in use for biliary infections; high concentrations of Amoxicillin are found in the bile of patients w/ normal biliary function
  • Ampicillin/sulbactam is no longer an option for routine empiric therapy of IAI due to high resistance of community-acquired E coli
    • May be used in patients w/ community-acquired E faecalis infection
    • Part of the regimen option used in treating necrotizing enterocolitis in neonates
  • Ticarcillin/clavulanic acid is recommended as a single agent for the treatment of mild-moderate CA-IAI
    • Have a broad spectrum of activity among the commonly isolated Gram-positive cocci & Gram-negative bacilli in IAI
  • Piperacillin/tazobactam may be used as a single agent for the treatment of patients w/ severe CA-IAI & HA-IAI
    • May be used in patients w/ community-acquired E faecalis infection
  • Piperacillin/tazobactam & Ticarcillin/clavulanic acid are acceptable broad-spectrum antibiotics that may be used in pediatric patients
  • Patients w/ beta-lactam allergy may be given the following:
    • CA-IAI: Tigecycline or a combination of Levofloxacin/Gentamicin/Metronidazole
    • HA-IAI: Ciprofloxacin/Amikacin/Metronidazole/Vancomycin or Aztreonam/Amikacin/Metronidazole/Vancomycin or Tigecycline/Ciprofloxacin

Quinolones

  • Rapidly & almost entirely absorbed from GI tract, can be excreted through renal, hepatic or biliary excretion
    • Ciprofloxacin can reach high biliary concentration even in patients w/ obstruction
  • Ciprofloxacin or Levofloxacin may be used in combination w/ Metronidazole to empirically treat mild-moderate & severe CA-IAI
    • Ciprofloxacin plus Metronidazole may be used in pediatric patients w/ severe reaction to beta-lactams, may also be given to patients w/ HA-IAI
  • Moxifloxacin is active against aerobic, Gram-positive, & Gram-negative pathogens
    • Has good penetration into peritoneal exudates & abscess cavities
    • Appropriate for use in patients w/ mild-moderate CA-IAI as single-agent therapy & in cases of beta-lactam allergy
    • Not inferior to Ertapenem in patients w/ mild-severe complicated IAI (cIAI)
    • Similarly effective as the standard therapies for patients w/ cIAI
    • Also effective against B fragilis, suggesting its use even w/o anti-anaerobic agent but should be avoided in patients who have received quinolone therapy w/in the past 3 months
  • Oral Ciprofloxacin & Moxifloxacin & IV Levofloxacin plus Metronidazole may be given for the completion of antimicrobial course of recovering patients from IAI
  • Ciprofloxacin or Levofloxacin plus Metronidazole may be used for convalescent treatment of Pseudomonas, Enterobacter, Serratia, & Citrobacter sp in pediatric patients for oral step-down therapy

Tigecycline

  • Used for treatment of mild-moderate or complicated CA-IAI as single-agent therapy
    • May be used in patients w/ severe CA-IAI & HA-IAI in combination w/ Ciprofloxacin
  • Showed in vitro activity against anaerobic pathogens, Enterococci, numerous ESBL-producing Enterobacteriaceae & carbapenemase-producing Enterobacteriaceae, Acinetobacter sp, & Stenotrophomonas maltophilia
    • An alternative to cephalosporin or quinolone if prevalence of community-acquired ESBL or quinolone-resistant E coli is >20%
  • A very good option for biliary infections
    • Has the ability to establish very high biliary & fecal concentrations
  • In clinical trials, it showed comparable clinical efficacy & safety w/ Imipenem & Ceftriaxone plus Metronidazole regimen

Necrotizing Enterocolitis

  • Most common in premature infants & full-term babies w/ an additional stressful illness
  • Usually results in mucosal injury, pneumatosis intestinalis, bacterial overgrowth, & sepsis
  • Infant presents w/ increased episodes of apnea & bradycardia followed by abdominal distension, bloody stools, & bilious vomiting
  • Managed w/ fluid resuscitation, IV broad-spectrum antibiotics (may include antifungal agents), & bowel decompression
  • When there is evidence of bowel perforation, urgent or emergent surgical intervention (eg laparotomy or percutaneous drainage) should be done
  • Regimen options: Ampicillin, Gentamicin + Metronidazole; Ampicillin, Cefotaxime + Metronidazole; or Meropenem
    • For suspected MRSA, Vancomycin instead of Ampicillin may be used
    • If Gram stain or culture shows fungal infection, Fluconazole or Amphotericin B should be used
  • For children candidate for oral step-down therapy, intra-abdominal culture results should be considered to allow for the use of the narrowest-spectrum, best-tolerated, & safest oral agents
Community-acquired Intra-abdominal Infections (CA-IAI)
A. Extra-biliary Antimicrobial Therapy
Non-critical patients w/o risk factors for ESBL Co-amoxiclav or Ciprofloxacin w/ Metronidazole
Non-critical patients w/ risk factors for ESBL Ertapenem or Tigecycline
Critically ill patients w/o risk factors for ESBL Piperacillin/tazobactam
Critically ill patients w/ risk factors for ESBL Meropenem or Imipenem w/ or w/o Fluconazole
B. Biliary
Non-critical patients w/o risk factors for ESBL Co-amoxiclav or Ciprofloxacin w/ Metronidazole
Non-critical patients w/ risk factors for ESBL Tigecycline
Critically ill patients w/o risk factors for ESBL Piperacillin/tazobactam
Critically ill patients w/ risk factors for ESBL Piperacillin w/ Tigecycline w/ or w/o Fluconazole
Hospital-acquired Intra-abdominal Infections (HA-IAI)
Non-critical patients w/ risk factors for MDR bacteria Piperacillin w/ Tigecycline w/ Fluconazole
Critically ill patients w/ risk factors for MDR bacteria Piperacillin w/ Tigecycline w/ Echinocandin or Meropenem or Imipenem or Doripenem w/ Teicoplanin w/ Echinocandin
Modified from the 2013 World Society of Emergency Surgery (WSES) Guidelines for Management of Intra-abdominal Infections

Non-Pharmacological Therapy

Successful management of intra-abdominal infections (IAI) depends on timely hemodynamic resuscitation & support of vital organ function, early administration of appropriate antimicrobial agents, quick anatomic diagnosis & adequate source control

Hemodynamic Resuscitation

  • Depletion of volume is common in patients w/ fever aggravated by poor fluid intake due to nausea & vomiting & presence of ileus secondary to intra-abdominal inflammation
  • Rapid administration of adequate amounts of fluid are necessary to restore adequate intravascular volume to promote physiological stability
  • In patients w/ no signs of volume depletion, fluid resuscitation should begin as soon as the patient is suspected to have IAI
  • Fluid resuscitation should be started at once in hypotensive patients w/ septic shock
    • Patient w/ septic shock or organ failure should be given fluid therapy more aggressively
    • Early goal-directed resuscitation should be done w/in the 1st 6 hours
      • Administer either crystalloid or colloid
      • Fluid challenge to restore mean circulating filling pressure
      • Norepinephrine or Dopamine to maintain an initial target of mean arterial pressure (MAP) ≥65 mmHg
      • Dobutamine when cardiac output remains low even after fluid resuscitation & combined inotropic/vasopressor therapy
      • Stress-dose steroid therapy in poorly responsive blood pressure
    • Goals of initial resuscitation are central venous pressure (CVP) of 8-12 mmHg, mean arterial pressure (MAP) of >65 mmHg, hourly urine output of >0.5 mL/kg, & central venous or mixed venous O2 saturation of >70% or >65%, respectively

Surgical Intervention

  • Refers to all physical measures used to remove a focus of infection, to prevent ongoing microbial infection & to restore normal physiological function & anatomy
  • Choice of procedure should be based on the anatomical focus of infection, extent of peritoneal inflammation, patient’s generalized septic response & condition
    • Regardless of surgical technique performed, a complete peritoneal toilet must be done to remove source of infection
  • May be delayed for up to 1 day in patients who are hemodynamically stable provided that appropriate antibiotics are given & patients are monitored vigilantly
    • In patients w/ diffuse peritonitis, emergency surgical intervention should be performed at once while continuing all measures to make the patient hemodynamically stable
    • Source control may not be done in selected patients w/ minimal physiological derangement & have a well-circumscribed infection foci (eg periappendiceal or pericolonic phlegmon), may be managed w/ antibiotics alone & very close clinical follow-up
  • Factors that may cause source control failure include:
    • >24 hours delay before surgical intervention was performed
    • High degree of peritoneal involvement (secondary to persistent or recurrent IAI, failure of anastomosis, or formation of fistula)
    • APACHE II score of >15
    • Age >70 years
    • Presence of comorbidities
    • Poor nutritional status

Drainage

  • Abscesses or infected fluid is evacuated & controlled fistula or sinus is created
  • Drainage may be performed operatively or percutaneously or by other techniques (eg opening a wound or removing staples or sutures)
    • Percutaneous drainage (PD) using ultrasound or CT scan is preferred over surgical procedure, given that adequate drainage is possible & debridement or repair of structures are not needed
    • May be done as a temporary intervention when repair or debridement is indicated especially in critically ill patients
    • Operative drainage is indicated when PD is not possible to be performed or when it is unsuccessful

Debridement

  • Involves the physical removal of necrotic or infected tissue
  • May be done surgically or superficial tissues may be debrided using frequent dressing changes
    • Fibrin & necrotic tissue adhere to the dressing & are removed when the dressing is changed
  • May involve the excision of necrotic intestine, the clearance of feces or fibrin from the peritoneal cavity, & the excision of necrotic & infected retroperitoneal fat in patients w/ infected pancreas
  • There needs to be a clear demarcation between viable & nonviable tissue for successful debridement

Restoration of Function & Anatomy

  • Last step in the management of IAI & usually needs surgery
    • Eg closure of perforated gastric ulcer, resection of strangulated & perforated small bowel
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