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"Guidelines for the Selection of Anti-infective Agents for Complicated Intra-abdominal Infections"

update in progress
Published: Clinical Infectious Diseases ; 2010 ; 501 : 133 -164

Abstract

A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases–Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations. 

Full text

*Projected Publication, Winter 2018

Recommendations

Initial Diagnostic Evaluation

  1. Routine history, physical examination, and laboratory studies will identify most patients with suspected intra-abdominal infection for whom further evaluation and management is warranted (A-II).
  2. For selected patients with unreliable physical examination findings, such as those with an obtunded mental status or spinal cord injury or those immunosuppressed by disease or therapy, intra-abdominal infection should be considered if the patient presents with evidence of infection from an undetermined source (B-III).
  3. Further diagnostic imaging is unnecessary in patients with obvious signs of diffuse peritonitis and in whom immediate surgical intervention is to be performed (B-III).
  4. In adult patients not undergoing immediate laparotomy, computed tomography (CT) scan is the imaging modality of choice to determine the presence of an intra-abdominal infection and its source (A-II). Fluid Resuscitation
  5. Patients should undergo rapid restoration of intravascular volume and additional measures as needed to promote physiological stability (A-II).
  6. For patients with septic shock, such resuscitation should begin immediately when hypotension is identified (A-II).
  7. For patients without evidence of volume depletion, intravenous fluid therapy should begin when the diagnosis of intra-abdominal infection is first suspected (B-III).

Timing of Initiation of Antimicrobial Therapy

  1. Antimicrobial therapy should be initiated once a patient receives a diagnosis of an intra-abdominal infection or once such an infection is considered likely. For patients with septic shock, antibiotics should be administered as soon as possible (A-III).
  2. For patients without septic shock, antimicrobial therapy should be started in the emergency department (B-III).
  3. Satisfactory antimicrobial drug levels should be maintained during a source control intervention, which may necessitate additional administration of antimicrobials just before initiation of the procedure (A-I). Elements of Appropriate Intervention
  4. An appropriate source control procedure to drain infected foci, control ongoing peritoneal contamination by diversion or resection, and restore anatomic and physiological function to the extent feasible is recommended for nearly all patients with intra-abdominal infection (B-II).
  5. Patients with diffuse peritonitis should undergo an emergency surgical procedure as soon as is possible, even if ongoing measures to restore physiologic stability need to be continued during the procedure (B-II).
  6. Where feasible, percutaneous drainage of abscesses and other well-localized fluid collections is preferable to surgical drainage (B-II).
  7. For hemodynamically stable patients without evidence of acute organ failure, an urgent approach should be taken. Intervention may be delayed for as long as 24 h if appropriate antimicrobial therapy is given and careful clinical monitoring is provided (B-II).
  8. In patients with severe peritonitis, mandatory or scheduled relaparotomy is not recommended in the absence of intestinal discontinuity, abdominal fascial loss that prevents abdominal wall closure, or intra-abdominal hypertension (A-II).
  9. Highly selected patients with minimal physiological derangement and a well-circumscribed focus of infection, such as a periappendiceal or pericolonic phlegmon, may be treated with antimicrobial therapy alone without a source control procedure, provided that very close clinical follow-up is possible (B-II).

Microbiologic Evaluation

  1. Blood cultures do not provide additional clinically relevant information for patients with community-acquired intra-abdominal infection and are therefore not routinely recommended for such patients (B-III).
  2. If a patient appears clinically toxic or is immunocompromised, knowledge of bacteremia may be helpful in determining duration of antimicrobial therapy (B-III).
  3. For community-acquired infections, there is no proven value in obtaining a routine Gram stain of the infected material (C-III).
  4. For health care-associated infections, Gram stains may help define the presence of yeast (C-III).
  5. Routine aerobic and anaerobic cultures from lower-risk patients with community-acquired infection are considered optional in the individual patient but may be of value in detecting epidemiological changes in the resistance patterns of pathogens associated with community-acquired intra-abdominal infection and in guiding follow-up oral therapy (B-II).
  6. If there is significant resistance (ie, resistance in 10%–20% of isolates) of a common community isolate (eg, Escherichia coli) to an antimicrobial regimen in widespread local use, routine culture and susceptibility studies should be obtained for perforated appendicitis and other community-acquired intra-abdominal infections (B-III).
  7. Anaerobic cultures are not necessary for patients with community-acquired intra-abdominal infection if empiric antimicrobial therapy active against common anaerobic pathogens is provided (B-III).
  8. For higher-risk patients, cultures from the site of infection should be routinely obtained, particularly in patients with prior antibiotic exposure, who are more likely than other patients to harbor resistant pathogens (A-II).
  9. The specimen collected from the intra-abdominal focus of infection should be representative of the material associated with the clinical infection (B-III).
  10. Cultures should be performed from 1 specimen, provided it is of sufficient volume (at least 1 mL of fluid or tissue, preferably more) and is transported to the laboratory in an appropriate transport system. For optimal recovery of aerobic bacteria, 1–10 mL of fluid should be inoculated directly into an aerobic blood culture bottle. In addition, 0.5 mL of fluid should be sent to the laboratory for Gram stain and, if indicated, fungal cultures. If anaerobic cultures are requested, at least 0.5 mL of fluid or 0.5 g of tissue should be transported in an anaerobic transport tube. Alternately, for recovery of anaerobic bacteria, 1–10 mL of fluid can be inoculated directly into an anaerobic blood culture bottle (A-I).
  11. Susceptibility testing for Pseudomonas, Proteus, Acinetobacter, Staphylococcus aureus, and predominant Enterobacteriaceae, as determined by moderate-to-heavy growth, should be performed, because these species are more likely than others to yield resistant organisms (A-III).

Recommended Antimicrobial Regimens

The antimicrobials and combinations of antimicrobials detailed in Tables 2–4 are considered adequate for empiric treatment of community- and health care-associated intra-abdominal infection as indicated.

Community-Acquired Infection of Mild-to-Moderate Severity in Adults

  1. Antibiotics used for empiric treatment of community-acquired intra-abdominal infection should be active against enteric gram-negative aerobic and facultative bacilli and enteric gram-positive streptococci (A-I).
  2. Coverage for obligate anaerobic bacilli should be provided for distal small bowel, appendiceal, and colon-derived infection and for more proximal gastrointestinal perforations in the presence of obstruction or paralytic ileus (A-I).
  3. For adult patients with mild-to-moderate community-acquired infection, the use of ticarcillin-clavulanate, cefoxitin, ertapenem, moxifloxacin, or tigecycline as single-agent therapy or combinations of metronidazole with cefazolin, cefuroxime, ceftriaxone, cefotaxime, levofloxacin, or ciprofloxacin are preferable to regimens with substantial anti-Pseudomonal activity (Table 2) (A-I).
  4. Ampicillin-sulbactam is not recommended for use because of high rates of resistance to this agent among community-acquired E. coli (B-II).
  5. Cefotetan and clindamycin are not recommended for use because of increasing prevalence of resistance to these agents among the Bacteroides fragilis group (B-II).
  6. Because of the availability of less toxic agents demonstrated to be at least equally effective, aminoglycosides are not recommended for routine use in adults with community-acquired intra-abdominal infection (B-II).
  7. Empiric coverage of Enterococcus is not necessary in patients with community-acquired intra-abdominal infection (A-I).
  8. Empiric antifungal therapy for Candida is not recommended for adult and pediatric patients with community-acquired intra-abdominal infection (B-II).
  9. The use of agents listed as appropriate for higher-severity community-acquired infection and health care-associated infection is not recommended for patients with mild-to-moderate community-acquired infection, because such regimens may carry a greater risk of toxicity and facilitate acquisition of more-resistant organisms (B-II).
  10. For those patients with intra-abdominal infection of mild-to-moderate severity, including acute diverticulitis and various forms of appendicitis, who will not undergo a source control procedure, regimens listed for treatment of mild-to-moderate-severity infection are recommended, with a possibility of early oral therapy (B-III).

High-Risk Community-Acquired Infection in Adults

  1. The empiric use of antimicrobial regimens with broad-spectrum activity against gram-negative organisms, including meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, ciprofloxacin or levofloxacin in combination with metronidazole, or ceftazidime or cefepime in combination with metronidazole, is recommended for patients with high-severity community-acquired intra-abdominal infection, as defined by APACHE II scores 115 or other variables listed in Table 1 (Table 2) (A-I).
  2. Quinolone-resistant E. coli have become common in some communities, and quinolones should not be used unless hospital surveys indicate 190% susceptibility of E. coli to quinolones (A-II).
  3. Aztreonam plus metronidazole is an alternative, but addition of an agent effective against gram-positive cocci is recommended (B-III).
  4. In adults, routine use of an aminoglycoside or another second agent effective against gram-negative facultative and aerobic bacilli is not recommended in the absence of evidence that the patient is likely to harbor resistant organisms that require such therapy (A-I).
  5. Empiric use of agents effective against enterococci is recommended (B-II).
  6. Use of agents effective against methicillin-resistant S. aureus (MRSA) or yeast is not recommended in the absence of evidence of infection due to such organisms (B-III).
  7. In these high-risk patients, antimicrobial regimens should be adjusted according to culture and susceptibility reports to ensure activity against the predominant pathogens isolated in culture (A-III).

Health Care-Associated Infection in Adults

  1. Empiric antibiotic therapy for health care-associated intra-abdominal infection should be driven by local microbiologic results (A-II).
  2. To achieve empiric coverage of likely pathogens, multidrug regimens that include agents with expanded spectra of activity against gram-negative aerobic and facultative bacilli may be needed. These agents include meropenem, imipenemcilastatin, doripenem, piperacillin-tazobactam, or ceftazidime or cefepime in combination with metronidazole. Aminoglycosides or colistin may be required (Table 3) (B-III).
  3. Broad-spectrum antimicrobial therapy should be tailored when culture and susceptibility reports become available, to reduce the number and spectra of administered agents (B-III).

Antifungal Therapy

  1. Antifungal therapy for patients with severe community-acquired or health care-associated infection is recommended if Candida is grown from intra-abdominal cultures (B-II).
  2. Fluconazole is an appropriate choice for treatment if Candida albicans is isolated (B-II).
  3. For fluconazole-resistant Candida species, therapy with an echinocandin (caspofungin, micafungin, or anidulafungin) is appropriate (B-III).
  4. For the critically ill patient, initial therapy with an echinocandin instead of a triazole is recommended (B-III).
  5. Because of toxicity, amphotericin B is not recommended as initial therapy (B-II).
  6. In neonates, empiric antifungal therapy should be started if Candida is suspected. If C. albicans is isolated, fluconazole is an appropriate choice (B-II).

Anti-enterococcal Therapy

  1. Antimicrobial therapy for enterococci should be given when enterococci are recovered from patients with health care-associated infection (B-III).
  2. Empiric anti-enterococcal therapy is recommended for patients with health care-associated intra-abdominal infection, particularly those with postoperative infection, those who have previously received cephalosporins or other antimicrobial agents selecting for Enterococcus species, immunocompromised patients, and those with valvular heart disease or prosthetic intravascular materials (B-II).
  3. Initial empiric anti-enterococcal therapy should be directed against Enterococcus faecalis. Antibiotics that can potentially be used against this organism, on the basis of susceptibility testing of the individual isolate, include ampicillin, piperacillin-tazobactam, and vancomycin (B-III).
  4. Empiric therapy directed against vancomycin-resistant Enterococcus faecium is not recommended unless the patient is at very high risk for an infection due to this organism, such as a liver transplant recipient with an intra-abdominal infection originating in the hepatobiliary tree or a patient known to be colonized with vancomycin-resistant E. faecium (B-III).

Anti-MRSA Therapy

  1. Empiric antimicrobial coverage directed against MRSA should be provided to patients with health care-associated intra-abdominal infection who are known to be colonized with the organism or who are at risk of having an infection due to this organism because of prior treatment failure and significant antibiotic exposure (B-II).
  2. Vancomycin is recommended for treatment of suspected or proven intra-abdominal infection due to MRSA (A-III). Cholecystitis and Cholangitis in Adults
  3. Ultrasonography is the first imaging technique used for suspected acute cholecystitis or cholangitis (A-I).
  4. Patients with suspected infection and either acute cholecystitis or cholangitis should receive antimicrobial therapy, as recommended in Table 4, although anaerobic therapy is not indicated unless a biliary-enteric anastamosis is present (B-II).
  5. Patients undergoing cholecystectomy for acute cholecystitis should have antimicrobial therapy discontinued within 24 h unless there is evidence of infection outside the wall of the gallbladder (B-II).
  6. For community-acquired biliary infection, antimicrobial activity against enterococci is not required, because the pathogenicity of enterococci has not been demonstrated. For selected immunosuppressed patients, particularly those with hepatic transplantation, enterococcal infection may be significant and require treatment (B-III).

Pediatric Infection

  1. Routine use of broad-spectrum agents is not indicated for all children with fever and abdominal pain for whom there is a low suspicion of complicated appendicitis or other acute intra-abdominal infection (B-III).
  2. Selection of specific antimicrobial therapy for pediatric patients with complicated intra-abdominal infection should be based on considerations of the origin of infection (community vs health care), severity of illness, and safety of the antimicrobial agents in specific pediatric age groups (A-II).
  3. Acceptable broad-spectrum antimicrobial regimens for pediatric patients with complicated intra-abdominal infection include an aminoglycoside-based regimen, a carbapenem (imipenem, meropenem, or ertapenem), a β-lactam/β-lactamase-inhibitor combination (piperacillin-tazobactam or ticarcillin-clavulanate), or an advanced-generation cephalosporin (cefotaxime, ceftriaxone, ceftazidime, or cefepime) with metronidazole (Tables 2 and 5) (B-II).
  4. For children with severe reactions to β-lactam antibiotics, ciprofloxacin plus metronidazole or an aminoglycoside-based regimen are recommended (B-III).
  5. Necrotizing enterocolitis in neonates is managed with fluid resuscitation, intravenous broad-spectrum antibiotics (potentially including antifungal agents), and bowel decompression. Urgent or emergent operative intervention, consisting of either laparotomy or percutaneous drainage, should be performed when there is evidence of bowel perforation. Intra-operative Gram stains and cultures should be obtained (B-III).
  6. Broad-spectrum antibiotics that may be useful in neonates with this condition include ampicillin, gentamicin, and metronidazole; ampicillin, cefotaxime, and metronidazole; or meropenem. Vancomycin may be used instead of ampicillin for suspected MRSA or ampicillin-resistant enterococcal infection. Fluconazole or amphotericin B should be used if the Gram stain or cultures of specimens obtained at operation are consistent with a fungal infection (B-II).

Pharmacokinetic Considerations

  1. Empiric therapy of patients with complicated intra-abdominal infection requires the use of antibiotics at optimaldoses to ensure maximum efficacy and minimal toxicity and to reduce antimicrobial resistance (Tables 5 and 6) (B-II).
  2. Individualized daily administration of aminoglycosides according to lean body mass and estimated extracellular fluid volume is preferred for patients receiving these agents for intra-abdominal infection (B-III). Use of Microbiology Results to Guide Antimicrobial Therapy
  3. Lower-risk patients with community-acquired intra-abdominal infection do not require alteration of therapy if a satisfactory clinical response to source control and initial therapy occurs, even if unsuspected and untreated pathogens are later reported (B-III).
  4. If resistant bacteria were identified at the time of initial intervention and there are persistent signs of infection, pathogen-directed therapy is recommended for patients with lower severity disease (B-III).
  5. Use of culture and susceptibility results to determine antimicrobial therapy in high-severity community-acquired or health care-associated infection should be based on pathogenic potential and density of identified organisms (B-III).
  6. Microbes recovered from blood cultures should be assumed to be significant if they have established pathogenic potential or are present in ⩾2 blood cultures (A-I) or if they are recovered in moderate or heavy concentrations from samples obtained from drainage (B-II). Duration of Therapy for Complicated Intra-abdominal Infections in Adults
  7. Antimicrobial therapy of established infection should be limited to 4–7 days, unless it is difficult to achieve adequate source control. Longer durations of therapy have not been associated with improved outcome (B-III).
  8. For acute stomach and proximal jejunum perforations, in the absence of acid-reducing therapy or malignancy and when source control is achieved within 24 h, prophylactic anti-infective therapy directed at aerobic gram-positive cocci for 24 h is adequate (B-II).
  9. In the presence of delayed operation for acute stomach and proximal jejunum perforations, the presence of gastric malignancy or the presence of therapy reducing gastric acidity, antimicrobial therapy to cover mixed flora (eg, as seen in complicated colonic infection) should be provided (B-III).
  10. Bowel injuries attributable to penetrating, blunt, or iatrogenic trauma that are repaired within 12 h and any other intraoperative contamination of the operative field by enteric contents should be treated with antibiotics for ⩽24 h (A-I).
  11. Acute appendicitis without evidence of perforation, abscess, or local peritonitis requires only prophylactic administration of narrow spectrum regimens active against aerobic and facultative and obligate anaerobes; treatment should be discontinued within 24 h (A-I).
  12. The administration of prophylactic antibiotics to patients with severe necrotizing pancreatitis prior to the diagnosis of infection is not recommended (A-I).

Use of Oral or Outpatient Intravenous Antimicrobial Therapy

  1. For children and adults whose signs and symptoms of infection are resolved, no further antibiotic therapy is required (B-III).
  2. For adults recovering from intra-abdominal infection, completion of the antimicrobial course with oral forms of moxifloxacin, ciprofloxacin plus metronidazole, levofloxacin plus metronidazole, an oral cephalosporin with metronidazole, or amoxicillin-clavulanic acid (B-II) is acceptable in patients able to tolerate an oral diet and in patients in whom susceptibility studies do not demonstrate resistance (B-II).
  3. If culture and susceptibility testing identify organisms that are only susceptible to intravenous therapy, such therapy may be administered outside of the hospital (B-III).
  4. For children, outpatient parenteral antibiotic management may be considered when subsequent drainage procedures are not likely to be required but symptoms of ongoing intra-abdominal inflammation persist in the context of decreasing fever, controlled pain, ability to tolerate oral fluids, and ability to ambulate (B-II).
  5. For oral step-down therapy in children, intra-abdominal cultures at the time of the drainage procedure are recommended to allow for the use of the narrowest-spectrum, best-tolerated, and safest oral therapy. A second-or third-generation cephalosporin in combination with metronidazole, or amoxicillin-clavulanate, may be options if the isolated organisms are susceptible to these agents. Fluoroquinolones, such as ciprofloxacin or levofloxacin, may be used to treat susceptible Pseudomonas, Enterobacter, Serratia, and Citrobacter species (B-III). If ciprofloxacin or levofloxacin is used, metronidazole should be added.
  6. Drug susceptibility results of isolated gram-negative aerobic and facultative organisms, if available, should be used as a guide to agent selection in children and adults (B-III).
  7. Because many of the patients who are managed without a primary source control procedure may be treated in the outpatient setting, the oral regimens recommended (see recommendations 83 and 86) can also be used as either primary therapy or step-down therapy following initial intravenous antimicrobial therapy (B-III).

Suspected Treatment Failure

  1. In patients who have persistent or recurrent clinical evidence of intra-abdominal infection after 4–7 days of therapy, appropriate diagnostic investigation should be undertaken. This should include CT or ultrasound imaging. Antimicrobial therapy effective against the organisms initially identified should be continued (A-III).
  2. Extra-abdominal sources of infection and noninfectious inflammatory conditions should also be investigated if the patient is not experiencing a satisfactory clinical response to a microbiologically adequate initial empiric antimicrobial regimen (A-II).
  3. For patients who do not respond initially and for whom a focus of infection remains, both aerobic and anaerobic cultures should be performed from 1 specimen, provided it is of sufficient volume (at least 1.0 mL of fluid or tissue) and is transported to the laboratory in an anaerobic transport system (C-III). Inoculation of 1–10 mL of fluid directly into an an-aerobic blood culture broth bottle may improve yield.

Pathways for the Diagnosis and Management of Patients with Suspected Acute Appendicitis

  1. Local hospitals should establish clinical pathways to standardize diagnosis, in-hospital management, discharge, and out-patient management (B-II).
  2. Pathways should be designed by collaborating clinicians involved in the care of these patients, including but not limited to surgeons, infectious diseases specialists, primary care practitioners, emergency medicine physicians, radiologists, nursing providers, and pharmacists, and should reflect local resources and local standards of care (B-II).
  3. Although no clinical findings are unequivocal in identifying patients with appendicitis, a constellation of findings, including characteristic abdominal pain, localized abdominal tenderness, and laboratory evidence of acute inflammation, will generally identify most patients with suspected appendicitis (A-II).
  4. Helical CT of the abdomen and pelvis with intravenous, but not oral or rectal, contrast is the recommended imaging procedure for patients with suspected appendicitis (B-II).
  5. All female patients should undergo diagnostic imaging. Those of child-bearing potential should undergo pregnancy testing prior to imaging and, if in the first trimester of pregnancy, should undergo ultrasound or magnetic resonance instead of imaging ionizing radiation (B-II). If these studies do not define the pathology present, laparoscopy or limited CT scanning may be considered (B-III).
  6. Imaging should be performed for all children, particularly those aged <3 years, when the diagnosis of appendicitis is not certain. CT imaging is preferred, although to avoid use of ionizing radiation in children, ultrasound is a reasonable alternative (B-III).
  7. For patients with imaging study findings negative for suspected appendicitis, follow-up at 24 h is recommended to ensure resolution of signs and symptoms, because of the low but measurable risk of false-negative results (B-III).
  8. For patients with suspected appendicitis that can neither be confirmed nor excluded by diagnostic imaging, careful follow-up is recommended (A-III).
  9. Patients may be hospitalized if the index of suspicion is high (A-III).
  10. Antimicrobial therapy should be administered to all patients who receive a diagnosis of appendicitis (A-II).
  11. Appropriate antimicrobial therapy includes agents effective against facultative and aerobic gram-negative organisms and anaerobic organisms, as detailed in Table 2 for the treatment of patients with community-acquired intra-abdominal infection (A-I).
  12. For patients with suspected appendicitis whose diagnostic imaging studies are equivocal, antimicrobial therapy should be initiated along with appropriate pain medication and antipyretics, if indicated. For adults, antimicrobial therapy should be provided for a minimum of 3 days, until clinical symptoms and signs of infection resolve or a definitive diagnosis is made (B-III).
  13. Both laparoscopic and open appendectomy are acceptable procedures, and use of either approach should be dictated by the surgeon's expertise in performing that particular procedure (A-I).
  14. Nonoperative management of selected patients with acute, nonperforated appendicitis can be considered if there is a marked improvement in the patient's condition prior to operation (B-II).
  15. Nonoperative management may also be considered as part of a specific approach for male patients, provided that the patient is admitted to the hospital for 48 h and shows sustained improvement in clinical symptoms and signs within 24 h while receiving antimicrobial therapy (A-II).
  16. Patients with perforated appendicitis should undergo urgent intervention to provide adequate source control (B-III).
  17. Patients with a well-circumscribed periappendiceal abscess can be managed with percutaneous drainage or operative drainage when necessary. Appendectomy is generally deferred in such patients (A-II).
  18. Selected patients who present several days after development of an inflammatory process and have a periappendiceal phlegmon or a small abscess not amenable to percutaneous drainage may delay or avoid a source control procedure to avert a potentially more morbid procedure than simple appendectomy. Such patients are treated with antimicrobial therapy and careful inpatient follow-up, in a manner analogous to patients with acute diverticulitis (B-II).
  19. The use of interval appendectomy after percutaneous drainage or nonoperative management of perforated appendicitis is controversial and may not be necessary (A-II).

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