Fever and Abdominal Pain - Antibiotic Therapy

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               The majority of infections addressed in this chapter require surgical intervention and/or drainage. Surgical consultation is strongly encouraged. Two sets of blood cultures should be drawn prior to initiation of antibiotic therapy.

                The goals of antibiotic therapy for intra-abdominal infections that are to be treated by either percutaneous or operative intervention are: (1) to hasten the elimination of infecting microorganisms, (2) minimize the risk of recurrent intra-abdominal infection, (3) (perhaps) shorten the clinical manifestations of infection, and (4) limit the extension of abdominal wound infection (e.g., necrotizing fasciitis). In patients with localized abscesses, antibiotics reduce fever and other manifestations of systemic response, but only after a 24- to 36-hour interval. Antibiotics should be administered after fluid resuscitation has been initiated to restore adequate visceral perfusion and provide better drug distribution. Moreover, antimicrobial side effects may be exacerbated with impaired organ perfusion.

                The selection of antimicrobials must take into account not only the presumed microbiology but also the general location of the acquisition of the infection, the severity of the patient’s illness and recently used antibiotics. Those who are more severely ill, especially if in septic shock, should be treated more aggressively since the margin for error is very thin. In these grave situations, it is best to select agents with activity against the most concerning pathogens such as Pseudomonas aeruginosa or VRE. If the patient is in septic shock, it may be prudent to select two agents that have activity against P. aeruginosa in addition to covering for both VRE (with daptomycin, quinupristin-dalfopristin (Synercid) or linezolid) and anaerobes (metronidazole). If a patient is on or has recently been on antibiotics it should be assumed, at least initially, that the pathogens causing the intraabdominal infection are resistant to those recently used antimicrobials and these antibiotics should be avoided. Once cultures are available, antibiotic empiricism can be more accurately tailored.

                Although the appropriate role of anti-enterococcal therapy is controversial, most authorities believe that specific therapy directed towards this organism should be given only when Enterococci are the only organisms isolated from abdominal samples or are isolated from blood. Numerous prospective, blinded and randomized trials have compared regimens active against routine isolates of Enterococcus for community-acquired infections. In at least six of these studies, the comparator regimen did not have similar coverage. Nonetheless, none of these trials demonstrated an advantage to treatment for Enterococci. Routine coverage of Enterococcus is therefore not necessary for patients with community acquired intra-abdominal infections.

               Infections that are monomicrobial such as primary peritonitis or splenic or renal abscesses can be treated with a single antibiotic aimed at a specific pathogen. Polymicrobic infections often need several antibiotics each aimed at a different pathogen. For example the classic “surgical triple” antibiotic regimen of ampicillin, gentamicin and clindamycin prescribed for secondary peritonitis is aimed at enterococcus, aerobic GNR and anaerobes. Table 5 summarizes commonly used antibiotics that may cover aerobic GNR, anaerobes, enterococci and Pseudomonas species. Some drugs have activity against a single “column” of bacteria on Table 5 such as aminoglycosides against aerobic GNR. Other drugs cover more than one type of pathogen (the agent shows activity in more than one column on Table 5) and can be used singly as an equivalent of two or three antibiotics. For example, ampicillin-sulbactam will cover community acquired aerobic GNR, anaerobes and enterococci while piperacillin-tazobactam or imipenem-cilastatin can cover nosocomial aerobic GNR, anaerobes and most enterococci.

                Several attempts have been made to identify clinical features in patients with peritonitis that increases the risk of adverse outcomes. These analyses have identified parameters prognostic of mortality rather than the risk of recurrent infection, including higher APACHE II scores, poor nutritional status, significant cardiovascular disease, and inability to obtain adequate source control. Similarly, patient’s immunosuppressed by medical therapy for transplantation, cancer, or inflammatory disease should receive a broader spectrum of therapy. Patients with other acute and chronic diseases may also be immunosuppressed although this is difficult to define. For such patients, antimicrobial regimens with expanded spectra may be warranted, including meropenem, imipenem/cilastatin, piperacillin/tazobactam, a quinolone plus metronidazole, or a third/fourth generation cephalosporin plus metronidazole.

                Prolonged pre-hospital length of stay and prolonged (> 2 days) pre-operative antimicrobial therapy are significant predictors of failure due to recurrent infection, and suggest that organisms resistant to the standard empiric antimicrobial regimen may be responsible. Such patients should be treated for healthcare-associated infection. Appropriate regimens for such patients will mirror therapy provided for other ICU-acquired infections such as ventilator-associated pneumonia, and typically include a carbapenem and vancomycin (or coverage for VRE). Individual units may harbor multi-resistant organisms and require even more focused therapy.

               Candida species often colonize the bowel lumen. Empiric therapy for community acquired infections is generally not indicated. Consideration of adding fluconazole empirically may be considered for patients with nosocomial infection and those in septic shock. Candida albicans or other Candida species are cultured from about 20% of patients with acute perforations of the gastrointestinal tract. Even when fungi are recovered, antifungal agents are unnecessary unless the patient has recently received immunosuppressive therapy for neoplasm, transplantation, or inflammatory disease, or has post-operative or recurrent intra-abdominal infection. If Candida albicans is found, fluconazole is an appropriate therapy. For fluconazole-resistant Candida species, therapy with amphotericin B, echinocandins (caspofungin, anidulofungin, micafungin) or a triazole (voriconazole or posaconazole) is appropriate. The latter two agents cause substantially less toxicity than amphotericin B and should be utilized before amphotericin B.

               When selecting antibiotics for intraabdominal infections, it is often useful to think through the most likely pathogens (the columns across Table 5) and select a single antibiotic to treat each one. Then, if one wishes, the antibiotic “triple” can be consolidated into one or two agents that will cover all the presumed pathogens.

               Table 6 summarizes the antibiotic empiricism for diffuse peritonitis. Table 7 summarizes the empiricism for localized intra-abdominal infections. Hospital acquired infections are more often caused by resistant bacteria requiring more broad spectrum antibiotics. Those patients in septic shock due to an intra-abdominal infection should be treated most aggressively since the margin for error is thin. Several choices are given in each diagnosis to give the clinician options for patients with antibiotic intolerances. Keep in mind that there is no one correct antibiotic or combinations of antibiotics to treat these infections. There are many ways to skin a bacterium.

 

Duration of Therapy

               Antimicrobial therapy for established infections should be continued until resolution of clinical signs of infection occurs, including normalization of temperature and white blood cell count, and return of gastrointestinal function. The risk of subsequent treatment failure appears to be quite low in patients who have no clinical evidence of infection at the time of cessation of antimicrobial therapy.

               In patients who have persistent or recurrent clinical evidence of intra-abdominal infection after five to seven days of therapy, appropriate diagnostic investigation should be undertaken. This should include CT or ultrasound imaging, and antimicrobial therapy effective against the organisms initially identified should be continued. Patients with persistent or recurrent intra-abdominal infections will likely require additional intervention to achieve source control. If a patient has persistent clinical symptoms and signs, but no evidence of a new or persistent infection is uncovered after a careful investigation, termination of antimicrobial therapy is warranted. Therapy can be changed to oral antibiotics when patients are clinically improved and tolerating oral feeds.

Table 5: Relative activities1 of antimicrobial agents used to treat intra-abdominal infections

 

Non-Pseudomonas

Gram-Negative Aerobes

Gram-Negative Anaerobes

Pseudomonas aeruginosa

Enterococcus

Aminoglycoside

+++

-

+++

-

Amoxicillin / clavulanate

++

++

-

+++

Ampicillin

+

-

-

+++

Ceftazidime

+++

-

+++

-

Cefotetan

++

++

-

-

Cefpodoxime

++

-

-

-

Ceftriaxone

++

-

-

-

Ciprofloxacin

+++

-

++

-

Clindamycin

-

+++

-

-

Co-trimoxazole

++

-

-

-

Ertapenem

++

+++

-

-

Imipenem-cilastatin

+++

+++

+

++2

Meropenem

+++

+++

++

++

Metronidazole

-

+++

-

-

Moxifloxacin

+++

++

+

++

Piperacillin

++

++

++

++

Piperacillin / tazobactam

+++

+++

+++

+++

Vancomycin

-

-

-

+++

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Adapted from Medical Management of Infectious Diseases, Ed C Grace, Marcel Dekker, 20031- No activity,  + Limited activity,  ++ Moderate activity,  +++   High activity,  2 activity against E. faecalis but not E. faecium

 

Table 6: Antibiotic empiricism for diffuse peritonitis

Clinical Diagnosis

Community Acquired

Hospital Acquired

Septic Shock

Primary Peritonitis

·  Ceftriaxone   OR

·  Levofloxacin   OR

·  Moxifloxacin   OR

·  Ampicillin-sulbactam   OR

·  Cotrimoxazole

·  Cefepime   OR

·  Levofloxacin

 

·  Cefepime    AND

·  Levofloxacin    AND

·  Vancomycin

Secondary Peritonitis

due to gastrointestinal perforation

·  Ampicillin-sulbactam   OR

·  Ertapenem   OR

·  Ceftriaxone 

 AND

Metronidazole

·  Cefepime   AND

    Metronidazole   AND

   Vancomycin  

OR

·  Piperacillin-tazobactam

OR

·  Imipenem-cilastatin

+/-

·  Fluconazole

·  Cefepime   AND

    Ciprofloxacin   AND

    Metronidazole   AND

    Vancomycin   AND

    Fluconazole

 

Table 7: Antibiotic empiricism for localized intra-abdominal infections
Clinical Diagnosis Community Acquired Hospital Acquired Septic Shock

Diverticulitis

·     Ampicillin-sulbactam  

OR

·        Ceftriaxone       AND

      Metronidazole    

OR

·        Ertapenem    

OR

·        Moxifloxacin

·        Cefepime     AND

       Metronidazole   AND

       Vancomycin     

OR

·        Piperacillin-tazobactam  

OR

·        Imipenem-cilastatin

·        Cefepime            AND

      Ciprofloxacin     AND

      Metronidazole    AND

      Vancomycin

Appendicitis

same as diverticulitis

same as diverticulitis

same as diverticulitis

Pancreatic abscess

same as diverticulitis

same as diverticulitis

same as diverticulitis

Cholecystitis

Cholangitis

same as diverticulitis

same as diverticulitis

same as diverticulitis

Hepatic abscess

same as diverticulitis

same as diverticulitis

same as diverticulitis

Splenic abscess

·        Vancomycin     AND

      Ceftriaxone      

OR

·        Ampicillin-sulbactam   

OR

·        Ertapenem

·        Vancomycin    AND

       Cefepime      

OR

·        Piperacillin-tazobactam  

OR

·        Imipenem-cilastatin

·        Vancomycin     AND

      Cefepime    

OR

·        Piperacillin-tazobactam 

OR

·        Imipenem-cilastatin

Colitis

·        Ciprofloxacin     

OR

·        Moxifloxacin    

OR

·        Co-trimoxazole    

OR

·        Metronidazole1

·        Metronidazole1

·        Metronidazole1

Pelvic Inflammatory Disease

·        Ampicillin-sulbactam    AND

      Doxycycline         

OR

·        Cefotetan      AND

      Doxycycline

OR

·        Levofloxacin     AND

      Metronidazole

·        Piperacillin-tazobactam   AND

      Doxycycline

OR

 ·        Levofloxacin            AND

       Metronidazole

·        Piperacillin-tazobactam  AND

      Doxycycline

OR

·        Levofloxacin      AND

      Metronidazole

Endometritis

·        Ceftriaxone    OR

      Gentamicin     AND

      Clindamycin 

OR

·        Ampicillin-sulbactam

 

·        Piperacillin-tazobactam

OR

·        Imipenem-cilastatin

·        Cefepime     AND

      Metronidazole    AND

      Vancomycin   

OR

·        Piperacillin-tazobactam 

   OR

 ·        Imipenem-cilastatin

Renal abscess

·        Ceftriaxone

·        Cefepime   AND

      Vancomycin

·        Cefepime     AND

      Ciprofloxacin    AND

      Vancomycin

Pyelonephritis

Same as renal abscess

Same as renal abscess

Same as renal abscess

1 for Clostridium difficile colitis