Bacterial Sepsis Treatment & Management

Early evaluation by a surgeon for patients with presumed intra-abdominal or pelvic sepsis is essential, because surgical intervention may be required for cure or resolution of the infection. For example, peritonitis may result in abscesses, which may subsequently need to be drained. Inadequate correction of intra-abdominal perforation or drainage procedures may result in a continuance or relapse of the patient’s septic condition.

The procedures used are dependent on the source of the infection, the severity of the sepsis, the patient’s clinical status, among other factors in individual scenarios.

Coordinate surgical follow-up with the surgeon.

Obtain a consultation with a surgeon for patients with presumed intra-abdominal or pelvic sepsis. Early surgical consultation and involvement by the surgical team is essential, because many causes of sepsis involve a perforated viscus, abscess, or obstructing process that requires surgical intervention for cure or resolution of the infection.

Also obtain a consultation with an infectious disease specialist for all patients with sepsis included in the differential diagnosis.^[31]

Early and aggressive medical therapy is indicated in patients with suspected sepsis.^{[28, 29, 30, 31, 32, 33, 34, 35, 36, 37]} However, it is crucial to consider pseudosepsis as a cause of the presenting syndrome complex because most causes of pseudosepsis are readily treatable and reversible if recognized and treated early. Patients with pseudosepsis require supportive therapy rather than antimicrobial treatment.

Patients with sepsis are generally ill and require bed rest or admission to the intensive care unit (ICU) for monitoring and treatment. Admission to an ICU or surgical ICU depends on the severity of the septic process and the degree of organ dysfunction, as well as the need for surgical intervention. Transfer to a facility able to perform diagnostic imaging tests or required surgical procedures if they are not available at the admitting hospital may be necessary.

Determine the likely source of the infection, and administer intravenous (IV) empiric antimicrobial agents until culture results become available, at which point more narrow-spectrum agents can be used (see below). In addition, offer supportive therapy aimed at maintaining organ perfusion, and provide respiratory support when necessary.^{[32, 38, 39]}

Most patients are instructed to take nothing by mouth and can tolerate a transient decrease in caloric intake over 1-2 weeks if their fluid and electrolyte balances are maintained.

Appropriate antimicrobial therapy depends on adequate coverage of the resident flora of the organ system presumed to be the source of the septic process.^{[28, 29, 30, 31, 40]} Agents suitable for empiric monotherapy regimens include the following:

• Imipenem
• Meropenem
• Cefoperazone (discontinued)
• Piperacillin-tazobactam
• Sulbactam-ampicillin

Combination therapeutic regimens include clindamycin or metronidazole plus levofloxacin, aztreonam, trimethoprim-sulfamethoxazole (TMP-SMZ), or an aminoglycoside.

No single drug or regimen is superior to another. Alternative agents may be used alone or in combination, provided that they have a low reactive potential and a good adverse-effect profile.^{[28, 29, 30, 31]}

Antibiotics are normally continued until the septic process and surgical interventions have controlled the source of infection. Ordinarily, patients are treated for approximately 2 weeks. As soon as patients are able to tolerate medications orally, they may be switched to an equivalent oral antibiotic regimen in an IV-to-oral conversion program.

A Cochrane review investigated potential use of deescalation to replace empirical broad-spectrum antimicrobial treatment with narrower antimicrobial therapy.^[41] This process involves either changing the agent or discontinuing combination treatment in accordance with the culture results. After examining 436 studies, the review determined that there is insufficient direct evidence to determine whether deescalation is effective or safe for adults with sepsis, severe sepsis, or septic shock. Further research using randomized, controlled trials is needed.

Empiric therapy for IV line infections

Because IV line infections are most often due to Staphylococcus aureus (methicillin-sensitive S aureus [MSSA] or methicillin-resistant S aureus [MRSA]) and less commonly due to aerobic gram-negative bacilli, the preferred empiric therapy for these infections is meropenem, cefoperazone (discontinued), or cefepime plus additional coverage for staphylococci.^{[12, 13]} If MRSA is prevalent in the institution, add linezolid, vancomycin, or daptomycin. MRSA infection appears to carry a high risk of inadequate treatment.^[42]

If coagulase-negative staphylococci are recovered from the blood (high-level bacteremia; that is, 3 or 4 positive blood cultures out of 4), avoid vancomycin for empiric therapy if possible; these are low-virulence organisms.

Treatment of coagulase-negative staphylococcal central line infection requires removal of the line. Vancomycin may be given, but central line removal is essential. If the central line cannot be removed for clinical reasons in a patient with MRSA or coagulase-negative staphylococcal infection, empiric suppressive vancomycin therapy is acceptable.

Minimize the use of vancomycin in order to prevent the emergence of Enterococcus faecium, a vancomycin-resistant species.^[12]

Empiric therapy for biliary tract infections

The main biliary tract pathogens include Escherichia coli, Klebsiella species, and Enterococcus faecalis. Coverage for staphylococci and anaerobes is not needed in the biliary tract. Anaerobes are important only in patients with diabetes who have Clostridium perfringens emphysematous cholecystitis. Preferred monotherapy regimens for biliary tract infections include imipenem, meropenem, piperacillin, or cefoperazone (discontinued).

Empiric therapy for intra-abdominal and pelvic infections

The main pathogens in the lower abdomen and pelvis include aerobic coliform gram-negative bacilli and B fragilis. Enterococci do not require special coverage. Potent anti– B fragilis and aerobic gram-negative bacillary coverage are essential, in addition to surgical intervention when drainage or repair of intra-abdominal viscera is required.

Preferred monotherapy regimens for intra-abdominal and pelvic infections include imipenem, meropenem, piperacillin-tazobactam, or ampicillin-sulbactam. Preferred combination therapy for intra-abdominal and pelvic infections consists of clindamycin or metronidazole plus aztreonam, levofloxacin, or an aminoglycoside.

Empiric therapy for urosepsis

The primary uropathogens include gram-negative aerobic bacilli, such as coliforms or enterococci (E faecalis, not E faecium vancomycin-resistant enterococci). Pseudomonas aeruginosa, Enterobacter species, and Serratia species are rare uropathogens and are associated with urologic instrumentation.

Preferred monotherapy for urosepsis due to aerobic gram-negative bacilli employs aztreonam, levofloxacin, third- or fourth-generation cephalosporins, or an aminoglycoside. However, preferred monotherapy for urosepsis due to enterococci (E faecalis) involves the use of ampicillin or vancomycin (penicillin-allergic).

Empiric therapy for community-acquired urosepsis consists of levofloxacin, aztreonam, or an aminoglycoside plus ampicillin. For nosocomial urosepsis, piperacillin, imipenem, or meropenem monotherapy is preferred.

Empiric therapy for staphylococcal, pneumococcal, and meningococcal sepsis

S aureus sepsis is usually associated with infection caused by devices or acute bacterial endocarditis. Empiric therapy may be with nafcillin, an antistaphylococcal agent, a cephalosporin, a carbapenem, linezolid, or clindamycin with or without rifampin.

Pneumococcal or meningococcal sepsis may be treated with penicillin G or a beta-lactam. In patients with associated meningococcal meningitis, the antibiotic selected should penetrate the cerebrospinal fluid (CSF) and should be given in meningeal doses.

Empiric therapy for sepsis of unknown origin

The usual sources of sepsis are the distal gastrointestinal (GI) tract, the pelvis, and the genitourinary (GU) tract. Organisms that should be covered from these areas include aerobic gram-negative bacilli (coliforms) and B fragilis. Enterococci are important pathogens in biliary tract sepsis and urosepsis.

Preferred empiric monotherapy includes meropenem, imipenem, piperacillin-tazobactam, or cefoperazone (discontinued).

Empiric combination therapy includes the following:

• Levofloxacin plus either clindamycin or metronidazole
• Aztreonam
• Cefepime plus either clindamycin or metronidazole
• Ceftriaxone or aminoglycoside plus metronidazole

Outpatient management

If orally administered antibiotics are continued at home, advise the patient about possible adverse effects. If additional antimicrobial therapy is needed outside the hospital setting, it should be given orally, not intravenously. Do not allow the total course of antibiotics to exceed 3 weeks, except for the treatment of liver abscesses, which may require prolonged courses of oral antibiotics for cure or complete clinical resolution.