Intra-abdominal%20infections Treatment

Successful management of intra-abdominal infection (IAI) depends on early recognition, timely hemodynamic resuscitation and support of vital organ function, early administration of appropriate antimicrobial agents, quick anatomic diagnosis and adequate source control, reevaluation of patient’s response and appropriate modification of treatment strategy

• Once there is a suspected IAI, it is proper to begin empiric antimicrobial therapy after blood and urine samples have been collected for culture
  
  • Initial antibiotic therapy for IAI is always empiric since patient is usually critically ill and that the results of culture and susceptibility take at least 48 hours to become available
  • Antibiotics should be started immediately, within 1 hour of recognition of septic shock or within 8 hours if with no hemodynamic or organ compromise
• Choice of antimicrobial drugs should be based on the possible organisms involved and risk factors for major resistance patterns, patient’s disease severity and risk for adverse outcomes, and 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, and proximal small bowel contain Gram-positive and Gram-negative facultative organisms
  • Infections that are from distal small bowel perforations contain Gram-negative facultative and aerobic organisms
    
    • These perforations typically evolve into localized abscesses and 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 and obligate anaerobic organisms; Streptococci and enterococci are commonly present
    
    • E coli is the most common Gram-negative facultative organism present
  • Enterobacteriaceae antibiotic resistance is high in Southeast Asia 
• 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, and therapy for ongoing infection
• In patients with severe CA-IAI and HA-IAI, culture and 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 with 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 with Piperacillin/tazobactam for 3 days
  • Residence in a long-stay care or nursing home and with an indwelling catheter and/or gastrostomy
  • Therapy during the preceding 3 months with a 3rd generation cephalosporin or fluoroquinolone

Pediatric Patients with IAI

• For children with fever and 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 versus HA-IAI), severity of the illness, and 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)

Necrotizing Enterocolitis

• Most common in premature infants and full-term babies with an additional stressful illness
• Usually results in mucosal injury, pneumatosis intestinalis, bacterial overgrowth, and sepsis
• Infant presents with increased episodes of apnea and bradycardia followed by abdominal distension, bloody stools, and bilious vomiting
• Managed with fluid resuscitation, IV broad-spectrum antibiotics (may include antifungal agents), and bowel decompression
• When there is evidence of bowel perforation, urgent or emergent surgical intervention (eg laparotomy or percutaneous drainage) should be done

Duration of Therapy

• Antibiotic treatment can be given for 2-3 days in localized CA-IAI, 5-7 days in generalized CA-IAI, and 5-15 days in postoperative or nosocomial IAI
  • An individualized approach should be done when deciding to continue, narrow or stop antibiotic treatment
• Antimicrobial therapy may be terminated with resolution of clinical signs of infection (eg absence of fever, normal white blood cell counts, decreasing inflammatory markers, tolerates oral diet); ICU patients with multiple organ failure may need 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 with acute perforations in the stomach and proximal jejunum or patients with cancer, and if source control was done within 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 within 12 hours and to those who had intraoperative contamination of the operative field
• Treatment of acute appendicitis with no perforation, abscess, or local peritonitis with narrow-spectrum regimen active against aerobic, facultative and obligate anaerobes should be discontinued within 24 hours

Mild-Moderate CA-IAI

• Antibiotics should have a coverage against enteric Gram-negative aerobic and facultative bacilli, and enteric Gram-positive Streptococci
• Obligate anaerobic bacilli should be covered in infections involving the distal small bowel, appendix and colon, and for proximal gastrointestinal perforations with obstruction or paralytic ileus
• Oral regimen is reasonable for patients with mild-moderate CA-IAI who are not at risk for an antibiotic-resistant organism infection and when the susceptibility of E coli to the drug in the community and hospital is >90%
• Ampicillin/sulbactam or Cefotetan, Cefoxitin and Clindamycin are not recommended for use because of high resistance rates to E coli and B fragilis, respectively
• Empiric coverage of Enterococcus and Candida is not necessary in mild-moderate CA-IAI
• Routine use of aminoglycosides in adults is not advised because of the availability of less toxic drugs

Severe CA-IAI

• Use of agents effective against enterococci is recommended
  • May consider using Ampicillin in patients at high risk for enterococci infection if not receiving treatment with Piperacillin/tazobactam or Imipenem/cilastatin  
• Consider giving a carbapenem if patient is at risk for infection with an ESBL-producing organism
• Vancomycin with Aztreonam and Metronidazole may be an alternative regimen for patients who cannot use carbapenems or beta-lactams  
• Quinolones should only be used if hospital survey indicates >90% quinolone susceptibility of E coli
• Agents against Methicillin-resistant S aureus (MRSA) or yeast are not advised unless infection due to such pathogens are present
• Piperacillin/tazobactam with or without Gentamicin can be given in critically ill patients
• Antifungal therapy is typically not recommended for CA-IAI unless the patient is critically ill or is concurrently receiving immunosuppressive therapy, eg chemotherapeutic agents, glucocorticosteroids, and immunomodulators
  • May be given in patients with severe community-acquired or postoperative peritonitis with at least 3 of the following criteria: Female, antibiotic therapy >48 hours, hemodynamic failure, or upper GI surgery
  • Echinocandins are appropriate for critically ill patients with CA-IAI

HA-IAI

• Agents to be used should have a wide spectrum of activity against Gram-negative aerobic and facultative bacilli
• Anti-enterococcal therapy is recommended especially in patients with postoperative infection, have recently received cephalosporins or other antibiotic against Enterococcus sp, immunocompromised, and with valvular heart disease or prosthetic intravascular materials
  • Initial empiric antibiotic should be against E faecalis, which includes Ampicillin, Piperacillin/tazobactam, and Vancomycin
  • Agent against Vancomycin-resistant E faecium is not recommended unless patient is a liver-transplant recipient with IAI that originates from hepatobiliary tree or the patient is known to be colonized with such pathogen
• Anti-MRSA agents are advised to patients with HA-IAI who are known to be colonized with the pathogen or to patients with prior treatment failure and significant antibiotic exposure
  
  • Vancomycin is the treatment of choice for treating suspected or proven IAI secondary to MRSA 
• Consider giving a carbapenem if patient is at risk for infection with an ESBL-producing organism  
• Antifungal therapy in adults is recommended for those with recent abdominal surgery, anastomotic leak, necrotizing pancreatitis, or upper GI or recurrent bowel perforations who are not improving despite antibacterial treatment  
  • Fluconazole is the treatment of choice if C albicans is isolated  
  • For Fluconazole-resistant Candida sp and in critically ill patients awaiting susceptibility testing results, echinocandin (eg Caspofungin, Micafungin, Anidulafungin) is recommended  
  • Amphotericin B is not an option for initial therapy due to its toxic effects
• Consider using antibiotic combinations with Amikacin in patients with confirmed allergy to beta-lactams 
• High risk of MDR bacteria exists in the 1st episode of HA-IAI with antibiotic therapy during 3 months prior to hospitalization and/or >2 days before 1st infectious episode and/or an interval of >5 days between the 1st surgery and reoperation

Pediatric Patients with IAI

• Broad-spectrum antimicrobial regimens that may be used in pediatric patients include:
  • Aminoglycoside-based regimen (may be an option in children with 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 with severe reactions to beta-lactams

Necrotizing Enterocolitis

• 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, and safest oral agents

Recommended Empirical Antibiotics for 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 with ototoxicity and nephrotoxicity, and have a narrow therapeutic range
  
  • Newer non-aminoglycoside agents have been found to be equally effective but without the associated toxicities of the aminoglycosides
  • Therefore, these agents should not be considered 1st-line agents and should be reserved for patients that have failed with other therapies or have severe allergic reactions to other antimicrobials
• Aminoglycoside-based regimens are acceptable options for use in pediatric patients with IAI and in selected HA-IAI patients depending on local susceptibility patterns
• May be added to the antibiotic regimen of severely ill patients and to those with previous long hospital stay or exposure to antibiotics to increase antibiotic coverage and 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 with other agents to treat patients with CA-IAI, or HA-IAI and necrotizing enterocolitis in neonates
• Clindamycin
  
  • B fragilis groups have shown resistance to Clindamycin and therefore, it may no longer be an acceptable anti-anaerobic agent for IAI

Aztreonam

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

Carbapenems

• May be used if prevalence of hospital-acquired, ESBL-producing organisms is >20%
• Ertapenem is appropriate for use in patients with mild-moderate CA-IAI as single-agent therapy and acceptable broad-spectrum antibiotic for use in pediatric patients
  
  • Has activity against ESBL-producing organisms but no activity against Pseudomonas spp and Enterococcus
  • Has a broad spectrum of activity against the commonly isolated Gram-positive cocci and Gram-negative bacilli in IAI
• Meropenem, Imipenem, Doripenem may be used for severe CA-IAI and HA-IAI
  
  • Have activity against non-fermentative Gram-negative bacilli
• Meropenem, Imipenem, or Ertapenem are acceptable options for use in pediatric patients with 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, and anaerobic organisms

Cephalosporins

• Cefoxitin monotherapy is appropriate for use in patients with mild-moderate CA-IAI
  
  • May be used in pediatric patients being evaluated and observed for appendicitis
• Cefazolin, Cefuroxime, Ceftriaxone and Cefotaxime in combination with Metronidazole are appropriate regimens for mild-moderate CA-IAI
  
  • Ceftriaxone and Cefotaxime in combination with 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 and Ceftazidime in combination with Metronidazole are recommended for patients with high-severity CA-IAI and HA-IAI
  
  • One of the acceptable broad-spectrum antibiotics used in pediatric patients in combination with Metronidazole
• Consider E coli resistance to 3rd generation cephalosporin if there is >10% local resistance or patient has spent time in areas with high prevalence of MDR bacteria
• Ceftazidime/avibactam and Ceftolozane/tazobactam combined with Metronidazole may be given to cIAI caused by mixed flora including antibiotic-resistant P aeruginosa or ESBL-producing organisms based on confirmed susceptibility testing  
  • Ceftazidime/avibactam is also active against many K pneumoniae carbapenemase-producing isolates while Ceftolozane/tazobactam shows excellent in vitro activity against MDR P aeruginosa

Penicillins with 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 with 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 with 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 and Gram-negative bacilli in IAI
• Piperacillin/tazobactam may be used as a single agent for the treatment of patients with severe CA-IAI and HA-IAI
  
  • May be used in patients with community-acquired E faecalis infection
• Piperacillin/tazobactam and Ticarcillin/clavulanic acid are acceptable broad-spectrum antibiotics that may be used in pediatric patients
• Patients with 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 and almost entirely absorbed from GI tract, can be excreted through renal, hepatic or biliary excretion
  
  • Ciprofloxacin can reach high biliary concentration even in patients with obstruction
• Ciprofloxacin or Levofloxacin should be used in combination with Metronidazole to empirically treat mild-moderate and severe CA-IAI
  
  • Ciprofloxacin plus Metronidazole may be used in pediatric patients with severe reaction to beta-lactams, may also be given to patients with HA-IAI
• Moxifloxacin is active against aerobic, Gram-positive, and Gram-negative pathogens
  
  • Has good penetration into peritoneal exudates and abscess cavities
  • Appropriate for use in patients with mild-moderate CA-IAI as single-agent therapy and in cases of beta-lactam allergy
  • Not inferior to Ertapenem in patients with mild-severe cIAI
  • Similarly effective as the standard therapies for patients with cIAI
  • Also effective against B fragilis, suggesting its use even without anti-anaerobic agent but should be avoided in patients who have received quinolone therapy within the past 3 months
• Oral Ciprofloxacin, Moxifloxacin or 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, and 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 with severe CA-IAI and HA-IAI in combination with Ciprofloxacin
• Showed in vitro activity against anaerobic pathogens, enterococci, numerous ESBL-producing Enterobacteriaceae and carbapenemase-producing Enterobacteriaceae, Acinetobacter sp, and 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 and fecal concentrations
• In clinical trials, it showed comparable clinical efficacy and safety with Imipenem and Ceftriaxone plus Metronidazole regimen

Hemodynamic Resuscitation

• Depletion of volume is common in patients with fever aggravated by poor fluid intake due to nausea and vomiting and 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 with 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 with septic shock
  
  • Patient with septic shock or organ failure should be given fluid therapy more aggressively
  • Early goal-directed resuscitation should be done within the 1st 6 hours
    
    • Administer either crystalloid or colloid solution
    • Fluid challenge to restore mean circulating filling pressure
• Vasopressors should be given if hypotension persists and fluid resuscitation fails to optimize blood flow 
  • Norepinephrine or Dopamine to maintain an initial target of mean arterial pressure (MAP) ≥65 mmHg
• Inotropic agents, eg Epinephrine or Dobutamine, may be given when cardiac output remains low even after fluid resuscitation and combined vasopressor therapy 
• Stress-dose steroid therapy in poorly responsive blood pressure
• Goals of initial resuscitation are central venous pressure (CVP) of 8-12 mmHg, MAP of >65 mmHg, hourly urine output of >0.5 mL/kg, and central venous or mixed venous O₂ saturation of >70% or >65%, respectively

• Refers to all physical measures used to remove a focus of infection, to prevent ongoing microbial infection and to restore normal physiological function and anatomy
• Choice of procedure should be based on the anatomical focus of infection, extent of peritoneal inflammation, patient’s generalized septic response and 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 and patients are monitored vigilantly
  
  • In patients with 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 with minimal physiological derangement and have a well-circumscribed infection foci (eg periappendiceal or pericolonic phlegmon), may be managed with antibiotics alone and very close clinical follow-up
• Factors that may cause source control failure include:
  
  • >24-hour 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 and 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 and debridement or repair of structures is 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 and necrotic tissue adhere to the dressing and are removed when the dressing is changed
• May involve the excision of necrotic intestine, the clearance of feces or fibrin from the peritoneal cavity, and the excision of necrotic and infected retroperitoneal fat in patients with infected pancreas
• There needs to be a clear demarcation between viable and nonviable tissue for successful debridement

Restoration of Function and Anatomy

• Last step in the management of IAI and usually needs surgery
  
  • Eg closure of perforated gastric ulcer, resection of strangulated and perforated small bowel, removal of infected appendix or gallbladder