SSC 2026 — Part 2: Infection — Antimicrobial Therapy & Source Control

This section covers infection management in adults with sepsis and septic shock, including the timing and approach to antimicrobial therapy stratified by diagnostic certainty, prehospital antibiotic administration, source control, empiric coverage for multidrug-resistant pathogens and anaerobic organisms, antifungal therapy, rapid diagnostic tests, prolonged beta-lactam infusion, therapeutic drug monitoring, antimicrobial de-escalation and discontinuation, and selective decontamination of the digestive tract.

Early administration of appropriate antimicrobial therapy is the most effective initial intervention to reduce mortality in patients with sepsis or septic shock, along with fluid resuscitation. Delivering antimicrobial therapy to patients with sepsis or septic shock should be treated as an emergency.

1. Timing of Antibiotic Initiation in Hospital

The SSC 2026 guidelines stratify antimicrobial timing recommendations by the likelihood of infection and severity of illness, using a standardized terminology framework:

Antimicrobial Timing Framework

Recommendation 16 — Definite/Probable Septic Shock: Immediate Antibiotics

For adults with possible, probable, or definite septic shock, we recommend administering antimicrobial therapy immediately, ideally within 1 hour of recognition.

Strong recommendation, very low certainty evidence

Change from 2021: Revisited.

Recommendation 17 — Probable/Definite Sepsis Without Shock

For adults with probable or definite sepsis without shock, we recommend administering antimicrobial therapy immediately, ideally within 1 hour of recognition.

Strong recommendation, very low certainty evidence

Change from 2021: Revisited.

Recommendation 18 — Possible Sepsis Without Shock

For adults with possible sepsis without shock, we suggest a time-limited course of rapid investigation and if concern for infection persists, the administration of antimicrobial therapy within 3 hours from the time when sepsis was first suspected.

Conditional recommendation, very low certainty evidence

Change from 2021: Revisited.

Recommendation 19 — Rapid Infectious vs. Noninfectious Assessment

Clinicians should perform a rapid assessment of the likelihood of infectious vs. noninfectious causes of acute illness in adults with possible sepsis without shock.

Good practice statement

Change from 2021: Revisited.

Recommendation 20 — Low Likelihood of Infection

For adults with a low likelihood of infection and without shock, we suggest deferring antimicrobial therapy while continuing to closely monitor the patient.

Conditional recommendation, very low certainty evidence

Change from 2021: Revisited.

Rationale for Recommendations 16–20: The panel identified a systematic review and meta-analysis which included 42 observational studies comprising 190,896 patients. Combined with two additional observational studies and two RCTs published after that meta-analysis, early antimicrobial therapy was associated with a reduction in short-term mortality for adults with sepsis or septic shock, including patients who received antibiotics within 1 hour (vs. longer), 3 hours (vs. longer), and 6 hours (vs. longer) from presentation, albeit with wide CIs that included no difference. This association was present in combined and separate analyses and appeared strongest and most consistent in patients with septic shock.

The two RCTs did not show an association between early treatment and reduced mortality but they primarily included patients without septic shock, and the median differences in time-to-antibiotics between the early vs. later antibiotic arms were well under 3 hours. Approximately 10–30% of patients initially treated for sepsis have a final diagnosis of noninfectious conditions.

2. Prehospital Antibiotics

Recommendation 21 — Prehospital Antimicrobial Administration

For adults with definite or probable sepsis and hypotension (i.e., septic shock) and who have an anticipated time to in-hospital medical evaluation of over 60 minutes, we suggest administering antimicrobial therapy in ambulance or flight.

Conditional recommendation, very low certainty evidence

Change from 2021: New.

Rationale: Three systematic reviews evaluated the impact of prehospital IV antibiotics on survival. Most studies were observational. Meta-analysis of observational studies was uncertain but suggested a possible reduction in mortality with prehospital antibiotics (OR 0.58; 95% CI, 0.41–0.84, very low certainty). Meta-analysis of RCTs also suggested that prehospital antibiotics may reduce 28-day mortality (OR 0.85; 95% CI, 0.66–1.09, low certainty).

The panel tailored this recommendation to patients with evidence of septic shock (SBP < 90; MAP < 65; SBP < 100 in patients with known hypertension). In EMS systems with short transport times and rapid hospital antibiotic delivery, prehospital antibiotics may have limited benefit.

Remark: Prehospital antibiotic delivery should be implemented only after having a structured process in place to screen for sepsis in ambulance or flight.

3. Biomarker-Guided Initiation

Recommendation 22 — Procalcitonin for Initiation Decisions

For adults with possible or probable sepsis or septic shock, we suggest using clinical evaluation alone over procalcitonin plus clinical evaluation to decide whether to start antimicrobial therapy.

Conditional recommendation, very low certainty evidence

Change from 2021: Carryover.

4. Source Control

Recommendation 23 — Emergent Source Control Evaluation

Adults with sepsis or septic shock should be rapidly evaluated for specific anatomical diagnoses or sources of infection that require emergent source control.

Good practice statement

Change from 2021: Carryover.

Recommendation 24 — Early Source Control

For adults with sepsis or septic shock and a specific anatomical diagnosis or source of infection that requires source control, we suggest early source control over late source control, ideally within 6 hours of diagnosis of sepsis or septic shock requiring source control.

Conditional recommendation, very low certainty evidence

Change from 2021: Revisited.

Rationale: Source control is a fundamental principle in the management of sepsis and septic shock. It encompasses surgical and procedural interventions to remove the source of infection, reduce the pathogen burden, or correct anatomical issues that impede normal clearance of infection. Common foci amenable to source control include:

• Intra-abdominal abscesses
• Peritonitis due to gastrointestinal perforation
• Cholangitis, cholecystitis
• Pelvic abscesses
• Pyelonephritis associated with obstruction or abscess
• Necrotizing soft-tissue infection
• Other deep space infections (empyema, septic arthritis)
• Infections related to implanted devices including central catheters

Meta-analysis of 11 relevant observational studies yielded uncertain findings (very low certainty evidence). However, point estimates suggest early source control may possibly reduce short-term (up to day 90) mortality (RR 0.70; 95% CI, 0.51–0.95, very low certainty) and may result in a large reduction in one-year mortality (RR 0.80; 95% CI, 0.71–0.95, very low certainty).

5. Empiric Multidrug Resistant (MDR) Pathogen Coverage

Recommendation 25 — High Risk of MDR Infection

For adults with sepsis or septic shock at high risk of infection with a specific multidrug resistant (MDR) pathogen, we suggest using empirical antimicrobial therapy with coverage for this MDR pathogen.

Conditional recommendation, very low certainty evidence

Change from 2021: New.

Recommendation 26 — Low Risk of MDR Infection

For adults with sepsis or septic shock at low risk of infection with a specific multidrug resistant (MDR) pathogen, we suggest against using empirical antimicrobial therapy with coverage for this MDR pathogen.

Conditional recommendation, very low certainty evidence

Change from 2021: New.

Rationale: MDR pathogens — defined as those with acquired non-susceptibility to at least one agent in three or more antimicrobial categories — include Acinetobacter baumannii, ESBL-producing Gram-negative bacteria, carbapenem-resistant Enterobacterales (CRE), vancomycin-resistant Enterococcus, MDR Pseudomonas, and methicillin-resistant S. aureus (MRSA).

Risk factors for MDR pathogens include:

• Colonization with the MDR pathogen of concern
• Previous infection with the MDR pathogen of concern in the prior year
• Prolonged use of broad-spectrum antibiotics
• Prolonged hospitalization in a unit with high prevalence of the MDR pathogen of concern

Meta-analysis yielded very low certainty evidence but suggested a possible reduction in short-term mortality with MDR coverage compared with no MDR coverage (OR 0.71; 95% CI, 0.56–0.92, very low certainty). This effect was driven by observational data evaluating MRSA infection. There was no observed difference for A. baumannii, ESBL-producing Gram-negative bacteria, or CRE.

6. Empiric Antifungal Coverage

Recommendation 27 — Empiric Antifungal Therapy

For adults with sepsis or septic shock, we suggest against empirical antifungal therapy.

Conditional recommendation, low certainty evidence

Change from 2021: Revisited.

Remark: Empiric antifungal therapy should be considered on a case-by-case basis in selected patients with sepsis or septic shock and risk factors for fungal infection, including immunosuppression, prolonged use of antibiotics, prolonged hospitalization, and intra-abdominal sources of infection.

Rationale: Meta-analysis of seven RCTs including the EMPIRICUS trial suggested that there may be no important reduction in short-term mortality with empiric antifungal therapy compared with no antifungal therapy (RR 0.93; 95% CI, 0.66–1.32, low certainty). Antifungal therapy is associated with clinically important undesirable effects, including drug-drug interactions, nephrotoxicity, hepatotoxicity, hyponatremia, phototoxicity, visual disturbances, encephalopathy, peripheral neuropathy, and selection of resistant fungi.

7. Empiric Anaerobic Coverage

Recommendation 28 — No Risk Factors for Anaerobic Infection

For adults with sepsis or septic shock without risk factors for anaerobic infection, we suggest using an empiric antibiotic regimen without anaerobic coverage.

Conditional recommendation, very low certainty evidence

Change from 2021: New.

Recommendation 29 — Specific Risk Factors for Anaerobic Infection

For adults with sepsis or septic shock with specific risk factors for anaerobic infection, we suggest using an empiric antibiotic regimen that includes anaerobic coverage.

Conditional recommendation, very low certainty evidence

Change from 2021: New.

Risk factors for anaerobic infection include:

• Intra-abdominal or deep seated gynecological/obstetric source of infection
• Necrotizing soft-tissue infection
• Head and neck infection
• Empyema
• CNS abscesses

Remark: When coverage of potential MDR pathogens is required, agents with anaerobic activity (e.g., piperacillin-tazobactam or carbapenems) are appropriate when alternative agents lacking anaerobic coverage are insufficient.

8. Microbiological Surveillance

Recommendation 30 — Surveillance Cultures to Guide Empiric Therapy

There is insufficient evidence to make a recommendation regarding use of departmental (i.e., ICU-wide) microbiological surveillance samples of the upper respiratory tract to guide empirical antimicrobial therapy.

No recommendation

Change from 2021: New.

9. Pathogen-Specific Rapid Diagnostic Tests

Recommendation 31 — Rapid Diagnostic Tests

For adults with sepsis or septic shock, we suggest using pathogen-specific rapid diagnostic tests on a case-by-case basis in selected patients based on clinical features, local pathogen- and resistance patterns, seasonality, and availability of tests and antibiotic stewardship guidance.

Conditional recommendation, low certainty evidence

Change from 2021: New.

Rationale: Pathogen-specific rapid diagnostic tests may include molecular PCR-based tests, phenotypic assays, respiratory and other syndromic panels, or antimicrobial resistance detection. A relevant systematic review and meta-analysis of 6 RCTs found possibly little to no difference in short-term mortality (RR 1.03; 95% CI, 0.78–1.13, low certainty). However, mortality benefits have been observed when rapid diagnostic tests are paired with effective antimicrobial stewardship programs.

10. Candida Fungal Biomarkers

Recommendation 32 — Candida Biomarkers for Initiation of Antifungal Therapy

For adults with sepsis or septic shock, we suggest against using Candida fungal biomarkers to guide initiation of empiric antifungal therapy.

Conditional recommendation, low certainty evidence

Change from 2021: New.

Remark: Use of Candida biomarkers to guide initiation of empiric antifungal therapy may be considered on a case-by-case basis in selected patients at high risk of Candida infection, including those with immunosuppression, prolonged exposure to antibiotics, prolonged hospitalization, and intra-abdominal source of infection.

11. Prolonged Infusion of Beta-Lactam Antibiotics

Recommendation 33 — Prolonged Beta-Lactam Infusion

For adults with sepsis or septic shock, we recommend using prolonged infusion of beta-lactams for maintenance (after an initial loading dose) over bolus administration.

Strong recommendation, moderate certainty evidence

Change from 2021: Revisited (upgraded from conditional to strong recommendation).

Rationale: Key pharmacokinetic parameters of beta-lactam antibiotics can change in patients with sepsis and septic shock, potentially leading to sub-therapeutic concentrations. Unlike traditional intermittent bolus infusion (lasting 30 min or less), administering beta-lactam antibiotics via prolonged IV infusion — either as an extended infusion (over at least half of the dosing interval) or as a continuous infusion — maintains consistent beta-lactam concentrations that maximize the pharmacodynamics of these drugs. The shorter the half-life of the drug, the greater the impact of extended or continuous infusion on drug concentrations.

A recent systematic review and meta-analysis of 18 RCTs (9,108 participants), including the large international BLING III RCT, demonstrated that prolonged infusions reduce short-term mortality:

Prolonged infusion is a viable intervention when suitable IV access is available and when resources can ensure that the beta-lactam is infused over the required duration. Administering a loading dose of the antibiotic before prolonged infusion is crucial to avoid delays in reaching effective beta-lactam concentrations. Throughout therapy, both extended and continuous infusions will occupy a venous catheter lumen for a longer duration than intermittent infusions, making drug stability and drug-drug compatibility important considerations.

Prioritize prolonged infusion when using beta-lactams with a shorter half-life, particularly piperacillin-tazobactam and carbapenems, given the very high probability of mortality benefit.

12. Therapeutic Drug Monitoring (TDM)

Recommendation 34 — Antimicrobial TDM

For adults with sepsis or septic shock, we suggest using antimicrobial therapeutic drug monitoring (TDM) on a case-by-case basis in selected patients, based on clinical features, local pathogen- and resistance patterns, drug class, and availability of TDM.

Conditional recommendation, very low certainty evidence

Change from 2021: Revisited.

Rationale: Antimicrobial therapy is subject to changes in pharmacokinetic (PK) and pharmacodynamic (PD) properties in sepsis and septic shock, which may result in concentrations that are either too low (risking clinical failure) or too high (potentially leading to toxicity). Factors affecting antimicrobial concentrations include augmented renal clearance, acute kidney injury, hypoalbuminemia, RRT, extracorporeal life support, and other conditions.

Meta-analysis of eight RCTs (1,241 participants) with 6 trials assessing TDM of antibacterials and two trials assessing TDM of antifungals yielded uncertain results (very low certainty). However, point estimates suggested a possible reduction in short-term mortality with TDM (RR 0.92; 95% CI, 0.75–1.11).

13. Antimicrobial De-escalation and Discontinuation

Recommendation 35 — Continuous Re-evaluation

Clinicians should continuously reevaluate patients, search for alternative diagnoses, and discontinue empiric antimicrobial therapy if an alternative cause of illness is demonstrated or strongly suspected in adults with suspected sepsis or septic shock but unconfirmed infection.

Good practice statement

Change from 2021: Revisited.

Recommendation 36 — De-escalation with Confirmed Pathogen

For adults with sepsis or septic shock, we recommend de-escalation of antimicrobial therapy over no de-escalation when a confirmed microbiological diagnosis and susceptibility profile is available.

Strong recommendation, very low certainty evidence

Change from 2021: Revisited.

Remark: De-escalation involves discontinuing unnecessary antimicrobial therapy or narrowing the spectrum of antimicrobial agents where appropriate.

Recommendation 37 — De-escalation Without Identified Pathogen

For adults with sepsis or septic shock, we suggest de-escalation of antimicrobial therapy over no de-escalation when no pathogens are identified on final culture results.

Conditional recommendation, very low certainty evidence

Change from 2021: Revisited.

Rationale for De-escalation (Recs 36–37): Direct evidence from 26 studies including two RCTs yielded uncertain meta-analysis results (very low certainty). However, point estimates suggested a possible reduction in short-term mortality (RR 0.77; 95% CI, 0.64–0.92), ICU LOS, hospital LOS, and antimicrobial resistance (RR 0.71; 95% CI, 0.55–0.91) with de-escalation of empiric antimicrobial therapy.

Recommendation 38 — Candida Biomarkers for Discontinuation of Antifungal Therapy

For adults with sepsis or septic shock who are receiving empiric antifungal therapy, we suggest against use of Candida fungal biomarkers to guide discontinuation of empiric antifungal therapy.

Conditional recommendation, low certainty evidence

Change from 2021: New.

14. Duration of Antimicrobial Therapy

Recommendation 39 — Shorter Duration

For adults with an initial diagnosis of sepsis or septic shock and adequate source control, we suggest using shorter over longer duration of antimicrobial therapy.

Conditional recommendation, very low certainty evidence

Change from 2021: Carryover.

Rationale: Since 2021, the BALANCE trial comparing 7 vs. 14 days of antibiotic treatment for bloodstream infection was published, showing non-inferiority of a 7-day treatment duration — providing further support for shorter treatment durations.

Recommendation 40 — Procalcitonin-Guided Discontinuation

For adults with an initial diagnosis of sepsis or septic shock and adequate source control where optimal duration of therapy is unclear, we suggest using procalcitonin AND clinical evaluation to decide when to discontinue antimicrobial therapy over clinical evaluation alone.

Conditional recommendation, low certainty evidence

Change from 2021: Carryover.

Rationale: Since 2021, the ADAPT-Sepsis RCT provided additional evidence that procalcitonin can be used to safely reduce antibiotic duration in patients with sepsis.

15. Selective Decontamination of the Digestive Tract (SDD)

Recommendation 41 — SDD in Mechanically Ventilated Adults

In mechanically ventilated adults with sepsis or septic shock in units with a low prevalence of antimicrobial resistance, we suggest using selective decontamination of the digestive tract.

Conditional recommendation, moderate certainty evidence

Change from 2021: New.

Rationale: SDD is a preventive infection control strategy consisting of the administration of nonabsorbable, topical antimicrobial agents to the oropharynx and upper gastrointestinal tract (oropharyngeal decontamination), with the administration of a short-term course of broad-spectrum IV antimicrobial therapy in mechanically ventilated patients. The topical antimicrobial agents used typically include a polymyxin, tobramycin, and amphotericin B, targeting aerobic Gram-negative bacteria and fungi while sparing anaerobes.

An up-to-date systematic review and meta-analysis of 32 RCTs (24,389 participants) including the large international SuDDICU trial demonstrated:

Counter to concerns, SDD appeared to reduce antimicrobial resistance rates. The desirable effects appeared to be mainly driven by trials with individual patient randomization and those using SDD in combination with a broad-spectrum IV antimicrobial agent targeting aerobic Gram-negative bacteria.

The panel found it important to consider the local prevalence of antimicrobial resistance when deciding on SDD, as the balance between desirable and undesirable effects may be different in settings with a high vs. low prevalence of antimicrobial resistance. In low resource settings where prevalence of antimicrobial resistance is high and there is limited availability of antimicrobial therapy, SDD should be implemented on an ICU-by-ICU basis.

The SuDDICU trial was published after SSC guideline recommendations were finalized. In this trial, randomization to SDD was associated with similar 90-day mortality (27.9% vs. 29.5%), fewer new blood stream infections (4.9% vs. 6.9%), and fewer antibiotic-resistant organisms cultured (16.8% vs. 26.8%).

Quick Reference: Infection Management Summary

INFECTION — AT A GLANCE

A. ANTIMICROBIAL TIMING
   ✓✓ Septic shock (possible/probable/definite): immediately, ≤ 1 hr    [Strong]
   ✓✓ Sepsis without shock (probable/definite): immediately, ≤ 1 hr     [Strong]
   ✓  Possible sepsis without shock: assess within 3 hr, treat if concern persists  [Conditional]
   GPS Rapidly assess infectious vs noninfectious causes                 [GPS]
   ✓  Low likelihood of infection: defer antibiotics, monitor            [Conditional]
   ✓  Prehospital antibiotics if shock + transport > 60 min              [Conditional]
   ✓  Use clinical evaluation alone over PCT to decide initiation        [Conditional]

B. SOURCE CONTROL
   GPS Rapidly evaluate for anatomical sources requiring intervention    [GPS]
   ✓  Early source control, ideally within 6 hours                       [Conditional]

C. EMPIRIC COVERAGE
   ✓  MDR coverage if high risk for specific MDR pathogen                [Conditional]
   ✗  No MDR coverage if low risk for MDR pathogen                       [Conditional against]
   ✗  Against empiric antifungal therapy (consider case-by-case)         [Conditional against]
   ✗  Against anaerobic coverage without risk factors                    [Conditional against]
   ✓  Anaerobic coverage if specific risk factors present                [Conditional]
   —  Surveillance cultures: insufficient evidence                       [No rec]
   ✓  Pathogen-specific rapid diagnostics: case-by-case                  [Conditional]
   ✗  Against Candida biomarkers for antifungal initiation               [Conditional against]

D. OPTIMIZATION
   ✓✓ Prolonged beta-lactam infusion (after loading dose)                [Strong] ⬆ UPGRADED
   ✓  Therapeutic drug monitoring on case-by-case basis                  [Conditional]

E. DE-ESCALATION & DURATION
   GPS Continuously re-evaluate and stop antibiotics if alternative dx   [GPS]
   ✓✓ De-escalate when confirmed pathogen + susceptibilities available    [Strong]
   ✓  De-escalate when no pathogens identified on final culture          [Conditional]
   ✗  Against Candida biomarkers for antifungal discontinuation          [Conditional against]
   ✓  Shorter over longer duration with adequate source control          [Conditional]
   ✓  PCT + clinical evaluation to guide discontinuation                 [Conditional]

F. DECONTAMINATION
   ✓  SDD in mechanically ventilated patients (low AMR prevalence)       [Conditional]

KEY: ✓✓ = Strong recommendation | ✓ = Conditional for | ✗ = Conditional against
     GPS = Good practice statement | — = No recommendation
     ⬆ = Upgraded from 2021

References