Bacterial Sepsis Treatment & Management

Updated: Feb 03, 2023
  • Author: Amber Mahmood Bokhari, MBBS; Chief Editor: Michael Stuart Bronze, MD  more...
  • Print

Approach Considerations

Early aggressive medical therapy is indicated in patients with suspected sepsis. [30, 31, 48, 49, 50, 51, 52, 53, 54, 55]

Sepsis Treatment

Patients with sepsis are generally ill and require inpatient hospitalization or admission to the intensive care unit (ICU) for monitoring and treatment. Admission to an ICU depends on the severity of the septic process and the degree of organ dysfunction. In July 2018, the US Centers for Medicare and Medicaid Services (CMS) began public reporting of a national sepsis bundle quality measure, commonly referred to as SEP-1. Early data demonstrated that only half of sepsis patients nationally received the full CMS-recommended bundle for emergency and hospital care. The treatment guidelines have been revised by IDSA/ Emergency Medicine Collaborative Task Force [56]  and Surviving Sepsis Campaign Guidelines 2021. [1]

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. [50, 57, 58]

A recent prospective study of 5787 adult patients with severe sepsis revealed the importance of goal-directed treatment. Patients triaged and managed according to 4 clinical goals (blood cultures before antibiotics, lactate before 90 minutes, IV antibiotics before 180 minutes, and 30 mL/kg of IV fluids before 180 minutes) were significantly less likely to die in the hospital than were those for whom all 4 of these goals were not met (22.6% vs 26.5%, respectively). [59]

In a multivariate regression analysis adjusted for age, admission to the intensive care unit (ICU), vasopressor initiation, central venous catheter insertion, and monitoring of central venous pressure and central venous oxygen saturation, complete compliance with the clinical goals was associated with a survival odds ratio of 1.194 (1.04-1.37). [59]


Surgical Intervention

Early evaluation in patients with presumed intra-abdominal or pelvic sepsis is essential, and surgical consultation should be obtained in appropriate patients.



Obtain a consultation with a surgeon for patients with presumed intra-abdominal or pelvic sepsis. Obtain a consultation with an infectious disease specialist, as indicated, in patients with presumed or proven sepsis. [30]


Antimicrobial Therapy

Appropriate antimicrobial therapy depends on adequate coverage of the bacteria associated with the specific organ or organ system associated with the infection. [30, 31, 32, 48, 49]  Agents suitable for empiric monotherapy regimens (depending on the source and underlying microbiology of the sepsis because the agent must be able to cover all of the likely pathogens) may include the following:

  • Imipenem
  • Meropenem
  • Tigecycline
  • Piperacillin-tazobactam
  • Ampicillin-sulbactam
  • Moxifloxacin

Combination therapeutic regimens include metronidazole plus either levofloxacin, aztreonam, a third- or fourth-generation cephalosporin, or an aminoglycoside.

Many advocate also using antistaphylococcal coverage (eg, vancomycin) empirically.

Although no drug regimen may be superior to another, time to first dose administration is very important. Mortality data suggest that early administration of appropriate antibiotics is correlated with better survival. Alternative agents may be used alone or in combination, with a good adverse-effect profile. [30, 31, 48, 49]

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, although duration may vary according to the source, site, and severity of the infection. 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.

Empiric therapy for IV line infections

A detailed discussion of catheter-associated infections is available in the IDSA catheter-associated line-related infections (CRBSI) guidelines. [60] IV line infections most often are due to Staphylococcus aureus (methicillin-sensitive S aureus [MSSA] or methicillin-resistant S aureus [MRSA]), but gram-negative bacilli can be involved. The preferred empiric therapy for these infections is meropenem or cefepime (for Pseudomonas) plus additional coverage for staphylococci. [37, 38] If MRSA is prevalent in the institution, add linezolid, vancomycin, or daptomycin. Otherwise, nafcillin, oxacillin, or cefazolin provide adequate coverage for MSSA.

Unless coagulase-negative, methicillin-sensitive staphylococci are recovered from the blood, with high-level bacteremia (3 or 4 positive blood cultures out of 4), avoid vancomycin for empiric therapy if possible; these are low-virulence organisms and may represent contaminants. If treatment is advised, the duration of therapy depends on the severity and site of infection. [60]

Treatment of staphylococcal central line infection and fungal or gram-negative organisms typically requires removal of the line.

Minimize the use of vancomycin in order to prevent the emergence of vancomycin-resistant enterococci (VRE). [37]

Empiric therapy for biliary tract infections

IDSA guidelines for complicated intra-abdominal infections such as biliary tract infections are available. [61] The main biliary tract pathogens include Escherichia coli, Klebsiella species, and Enterococcus faecalis. Coverage for staphylococci is not needed in the biliary tract. Anaerobes can also be important, especially in patients with diabetes or immunosuppression.

Preferred monotherapy regimens for biliary tract infections include imipenem, meropenem, ampicillin-sulbactam, or piperacillin-tazobactam. Cephalosporins or quinolones in combination with metronidazole are alternate first-line agents for the treatment of biliary tract infections.

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 unless the patient has recurrent infection or enterococci have been specifically and repeatedly isolated. 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, ampicillin-sulbactam, or tigecycline. Alternate combination therapy for intra-abdominal and pelvic infections consists of clindamycin or metronidazole plus a third- or fourth-generation cephalosporin, aztreonam, levofloxacin, or an aminoglycoside. Some authors raise concerns about the use of tigecycline.

Empiric therapy for urosepsis

The primary uropathogens include gram-negative aerobic bacilli, such as coliforms or enterococci. Pseudomonas aeruginosa, Enterobacter species, and Serratia species are rare uropathogens and are associated with urologic instrumentation.

Monotherapy for urosepsis due to aerobic gram-negative bacilli may include aztreonam, levofloxacin, a third- or fourth-generation cephalosporin, or an aminoglycoside. However, preferred monotherapy for enterococcal urosepsis involves ampicillin or vancomycin. For VRE urosepsis, linezolid or daptomycin may be used.

Empiric therapy for community-acquired urosepsis consists of levofloxacin, aztreonam, or an aminoglycoside plus ampicillin. For nosocomial urosepsis, a fourth-generation cephalosporin, piperacillin-tazobactam, imipenem, or meropenem, with or without an aminoglycoside, is preferred.

Empiric therapy for staphylococcal, pneumococcal, and meningococcal sepsis

S aureus sepsis is usually associated with infection caused by devices or bacterial endocarditis. Empiric therapy may be with an anti-staphylococcal penicillin (nafcillin or oxacillin), vancomycin, a cephalosporin, daptomycin, or linezolid, depending on the concern for MRSA.

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. Consider the regional prevalence of drug-resistant pneumococci when selecting an antibiotic.

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 tigecycline.

Empiric combination therapy includes metronidazole plus levofloxacin, aztreonam, or a third- or fourth-generation cephalosporin.

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 specific clinical scenarios, which may require prolonged courses of oral antibiotics for cure or complete clinical resolution.