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SULBACTAM SODIUM

Sulbactam sodium is most often studied as part of combination antibiotics (for example, with ampicillin, cefoperazone, ceftriaxone, piperacillin, or ceftazidime). Across the clinical trials provided, researchers have tested these sulbactam-containing treatments for different bacterial infections (like pneumonia, urinary infections, intra-abdominal infections, gonorrhea, and resistant Acinetobacter infections) and also studied safety topics such as side effects and blood-clotting problems. The trials also include “pharmacokinetic” studies, which measure drug levels in the blood or lungs to help choose the best dosing.

Table of Contents

1) What sulbactam sodium is in these trials

Across the included clinical trials, Sulbactam Sodium appears most often as part of combination antibiotic products rather than used alone, such as ampicillin sodium/sulbactam sodium (also called Unasyn-S) for pneumonia and other infections, or in combinations with cephalosporins like cefoperazone or ceftriaxone for different infectious diseases.[1][2][3]

There are also trials where sulbactam is studied in more advanced combinations aimed at resistant bacteria, including sulbactam paired with durlobactam (also known as ETX2514) and used with background antibiotics such as imipenem/cilastatin in hospitalized patients.[4][5]

2) How sulbactam-containing combinations are meant to work

Several trials explain that sulbactam works as a beta-lactamase inhibitor, meaning it blocks bacterial enzymes (beta-lactamases) that can break down certain antibiotics. By blocking these enzymes, sulbactam can help the partner antibiotic stay active and work better, especially in settings where bacteria have developed resistance.[6][7]

Some trials also highlight a special point: sulbactam itself is described as having distinctive activity against Acinetobacter spp., which is important because Acinetobacter (especially A. baumannii) is a major cause of serious hospital and ICU infections and is often resistant to many antibiotics.[8][9]

3) Conditions and infections studied

The trials cover a wide range of bacterial infections where sulbactam-containing regimens were tested for treatment or prevention. These include respiratory infections, urinary infections, abdominal infections, sexually transmitted infection (gonorrhea), and complicated ICU infections with resistant organisms.[1][6][3][4]

  • Community-acquired pneumonia (CAP): Studied with ampicillin/sulbactam regimens including 12 g/day dosing in Japanese adults and combination therapy with azithromycin plus ampicillin/sulbactam in hospitalized patients.[1][10]

  • Respiratory tract infections and urinary tract infections: Phase IV studies tested piperacillin/sulbactam and ceftriaxone/sulbactam in adults or children, focusing on cure and bacterial clearance rates.[6][7]

  • Complicated urinary tract infections (including acute pyelonephritis): Studied with sulbactam-ETX2514 added to background imipenem/cilastatin, with outcomes looking at combined clinical cure and microbiologic eradication.[5]

  • Intra-abdominal infections (including localized peritonitis) and related conditions: Comparative studies examined ampicillin/sulbactam vs other antibiotics (like moxifloxacin or ertapenem), and another trial collected outcomes for cefoperazone/sulbactam in serious hepatobiliary and intra-abdominal infections (including appendicitis, cholecystitis, abscess, wound infections, and peritonitis).[11][12][13]

  • Uncomplicated urogenital gonorrhea: A phase IV single-arm study evaluated ceftriaxone/sulbactam (CRO-SBT) for bacterial eradication and symptom resolution at the test-of-cure visit, including adolescents and adults (and weight-based dosing for children under 12).[3]

  • Complicated skin and skin structure infections: A multicenter trial compared tigecycline with comparator regimens including ampicillin/sulbactam (or amoxicillin/clavulanate) and allowed additional antibiotics if MRSA was suspected early on.[14]

4) How sulbactam was given (dose, schedule, IV methods)

Many trials used intravenous (IV) dosing, sometimes as standard infusions and sometimes as extended infusion (slow infusion over several hours). The goal of extended infusion is to keep antibiotic levels effective for longer periods, which can matter in severe infections or resistant bacteria.[8][5]

  • High-dose ampicillin/sulbactam (Unasyn-S) in CAP: 12 g/day (3 g four times daily) IV for 3 to 14 days was evaluated in Japanese adults for safety and effectiveness, because this high-dose regimen was used in other regions but not approved in Japan at the time of the study.[1]

  • High-dose real-world surveillance in Japan: A surveillance study tracked high-dose (>6 g/day) IV use of sulbactam/ampicillin for pneumonia, lung abscess, and peritonitis, with a stated maximum daily dose of 12 g (3 g four times daily).[2]

  • ICU Acinetobacter trial dosing examples: One randomized ICU study compared ampicillin/sulbactam vs cefoperazone/sulbactam, both given as 2 g IV every 8 hours with each dose infused over 4 hours (extended infusion), diluted in normal saline with specified maximum concentrations.[8]

  • Sulbactam alone for PK modeling in critically ill patients: A pharmacodynamics modeling study administered 2 g every 12 hours as a 1-hour infusion (in 100 mL normal saline) for 10 days, then measured blood levels on day 4 and used simulation methods to estimate target attainment.[9]

5) Outcomes used to judge success (clinical and lab)

Trials used both symptom-based and lab-based outcomes. Symptom-based outcomes included whether fever, symptoms, and exam findings improved, while lab outcomes included whether cultures became negative for the original bacteria.[1][3]

  • Clinical response / cure: Some pneumonia and infection trials used a response rate judged either by investigators or by a data review committee, typically at end of treatment and at test of cure follow-ups.[1]

  • Bacteriological eradication: Gonorrhea trials looked for culture-confirmed eradication of Neisseria gonorrhoeae at the urogenital site at TOC. Other infection trials looked for bacterial clearance/eradication in urine or respiratory samples.[3][5]

  • Composite “overall success”: In complicated UTI, a main endpoint was overall success combining clinical cure and microbiologic eradication in a defined analysis population.[5]

6) Safety topics studied (side effects and special risks)

Safety evaluation was a central part of many sulbactam-related trials, especially in higher-dose settings, ICU settings, and pharmacokinetic studies in healthy volunteers.[2][15]

  • Adverse events and serious adverse events: Multiple studies counted the number of participants experiencing side effects, including allergies, rash, shock, and death in some Phase IV infection-treatment studies, and broader AE/SAE tracking in Phase 1 PK studies.[6][15]

  • Unexpected adverse drug reactions: A Japanese surveillance study specifically aimed to detect adverse reactions not expected from the Japanese package insert and to identify factors affecting safety and effectiveness during high-dose use of Unasyn-S.[2]

  • Drug-induced coagulation disorder risk modeling: An epidemiology study focused on coagulation dysfunction after exposure to cefoperazone/sulbactam sodium, tracking tests like PT, APTT, TT, and platelet counts, and using logistic regression to build a prediction model for risk factors.[16]

  • Kidney toxicity (nephrotoxicity): In the sulbactam-durlobactam vs colistin study in ABC infections, nephrotoxicity was a primary safety endpoint measured using the RIFLE criteria.[4]

7) Pharmacokinetics and bioequivalence studies

Several trials examined how sulbactam-containing products behave in the body, which helps researchers understand dosing. These trials measured blood concentrations over time, including Cmax and AUC, and in some cases measured drug levels in lung-related compartments.[17][15]

  • Bioequivalence of cefoperazone/sulbactam products: One crossover study compared two formulations (Burotam vs Brosym) after IV infusion in healthy volunteers under fasting conditions, measuring Cmax and AUC values.[17]

  • Lung penetration measurements: A Phase 1 study measured sulbactam and ETX2514 concentrations in plasma, epithelial lining fluid (ELF), and alveolar macrophages using bronchoscopy with bronchoalveolar lavage at scheduled time points after dosing.[15]

8) Use in preventing infections around surgery and devices

Beyond treating infections, several trials studied sulbactam-containing antibiotics as antibiotic prophylaxis, meaning treatment given to prevent infections around operations or implanted devices.[18][19][20]

  • Laparoscopic cholecystectomy: A randomized trial compared prophylaxis with ampicillin/sulbactam vs ciprofloxacin vs placebo to reduce surgical site infection after elective laparoscopic gallbladder surgery.[18]

  • Acute calculous cholecystitis discharge antibiotics: Another study examined whether giving oral ampicillin/sulbactam after discharge (5–7 days) affected surgical site infection rates after laparoscopic cholecystectomy for acute calculous cholecystitis, following patients for a month and classifying SSIs using CDC categories.[21]

  • Cesarean section prophylaxis: Trials compared single-dose ampicillin/sulbactam with cefuroxime at cord clamping, and another study compared cefepime vs ampicillin/sulbactam (Unictam) given before and after cesarean delivery for prevention of post-cesarean SSIs.[19][22]

  • Cardiac implantable electronic devices (CIED): A double-blind randomized trial studied ampicillin/sulbactam given IV before implantation plus intrapocket dosing, then compared 3 days of IV ampicillin/sulbactam vs placebo after implantation, measuring device-related infection outcomes and biomarkers like presepsin, IL-6, and procalcitonin.[20]

9) Focus on resistant Acinetobacter infections

Several trials focus on difficult-to-treat infections caused by Acinetobacter baumannii or the Acinetobacter baumannii-calcoaceticus complex (ABC), especially in critically ill ICU patients, where resistance to many antibiotics is common.[8][4]

  • Comparing sulbactam-based regimens: One randomized controlled ICU study compared ampicillin/sulbactam vs cefoperazone/sulbactam for multidrug-resistant Acinetobacter baumannii infections, assessing clinical improvement and microbiological culture response on Day 5.[8]

  • New partner inhibitor: durlobactam (ETX2514): A major randomized study tested sulbactam-durlobactam with imipenem/cilastatin compared with colistin plus imipenem/cilastatin in ABC pneumonia or bacteremia, measuring 28-day all-cause mortality and kidney toxicity (nephrotoxicity) as primary endpoints.[4]

  • Pediatric dosing development: A Phase 1b pediatric study evaluated sulbactam-durlobactam dosing from birth to under 18 years, measuring PK values (like Cmax and AUC0-24) and tracking treatment-emergent adverse events plus lab changes (liver, kidney, blood counts, and vital signs).[23]

  • Combination strategies in CRAB: A protocol described a randomized ICU study comparing colistin combined with fosfomycin, ampicillin/sulbactam (with bolus plus continuous infusion up to 12 g/day), or eravacycline, using outcomes such as negative microbiological samples after 10 days and SOFA score reduction.[24]

  • Comparing cefiderocol + ampicillin/sulbactam to colistin-based regimens: A controlled study with historical controls planned to compare cefiderocol plus ampicillin/sulbactam against colistin (with or without meropenem) for CRAB bacteremia and hospital-acquired or ventilator-associated pneumonia, with all-cause mortality as the primary outcome.[25]

Main topic What the trials studied
Sulbactam sodium in clinical trials Mostly used in combination antibiotics (ampicillin/sulbactam, cefoperazone/sulbactam, ceftriaxone/sulbactam, piperacillin/sulbactam, ceftazidime/sulbactam) and also studied as sulbactam alone for PK/dosing modeling.
Infections treated Pneumonia (CAP, HABP/VABP), urinary tract infections (including complicated UTI and pyelonephritis), intra-abdominal infections (including peritonitis and abscess), gonorrhea, complicated skin infections, and resistant Acinetobacter infections in ICU settings.
Key effectiveness outcomes Clinical response/cure, bacterial eradication or clearance in cultures, surgical site infection rates, ICU outcomes such as mortality and SOFA score changes.
Key safety outcomes Adverse events and serious adverse events, nephrotoxicity using RIFLE criteria, allergic reactions, and a focused study on drug-induced coagulation disorders with cefoperazone/sulbactam.
How dosing was explored Single-dose studies, multi-day regimens, high-dose surveillance (up to 12 g/day for Unasyn-S in Japan), extended/continuous infusions, and PK/bioequivalence studies measuring Cmax and AUC.

FAQ

  • What is sulbactam sodium and why is it usually combined with another antibiotic? In these trials, sulbactam sodium is used mainly as a <b>beta-lactamase inhibitor</b>—meaning it helps protect certain antibiotics from being broken down by bacterial enzymes called beta-lactamases. This can make the partner antibiotic work better against resistant bacteria. Trials studied combinations such as ampicillin/sulbactam (Unasyn-S), cefoperazone/sulbactam, ceftriaxone/sulbactam (CRO-SBT), piperacillin/sulbactam, and ceftazidime/sulbactam.
  • Which infections were studied with sulbactam-containing treatments? Based on the trials provided, sulbactam-containing regimens were studied for: community-acquired pneumonia and other pneumonias; lung abscess; peritonitis and intra-abdominal infections (including appendicitis, cholecystitis, and intra-abdominal abscess); respiratory tract and urinary tract infections; uncomplicated urogenital gonorrhea; complicated urinary tract infections and acute pyelonephritis; complicated skin and skin structure infections; and serious infections caused by multidrug-resistant or carbapenem-resistant <b>Acinetobacter baumannii</b>.
  • How was effectiveness measured in these trials? Effectiveness was commonly measured using: <b>clinical response</b> (whether symptoms and exam findings improved), <b>bacterial eradication/clearance</b> (whether lab cultures no longer grew the bacteria), and infection-related outcomes such as surgical site infection rates after operations. Some studies focused on ICU outcomes like <b>SOFA score</b> changes (a score that tracks organ failure) and survival (mortality).
  • What dosing approaches were tested for sulbactam-containing therapies? Trials included single-dose IV treatments (for example, ceftriaxone/sulbactam in gonorrhea), multi-day IV regimens (such as ampicillin/sulbactam in pneumonia or intra-abdominal infection), and high-dose use (for example, Unasyn-S high-dose regimens up to 12 g/day in Japan). Some ICU studies used <b>extended infusion</b> (giving each dose slowly over several hours) or continuous infusions to keep drug levels steady.
  • What safety concerns were specifically studied with sulbactam combinations? Safety monitoring in these trials included tracking <b>adverse events</b> (side effects), serious adverse events, and special risks. One epidemiology study focused on <b>drug-induced coagulation disorder</b> (blood-clotting test abnormalities) associated with cefoperazone/sulbactam and aimed to build a risk-factor prediction model. Other studies tracked kidney and liver laboratory changes, allergic reactions, and nephrotoxicity using criteria like <b>RIFLE</b> in critically ill patients.

Ongoing Clinical Trials on SULBACTAM SODIUM

  • Study on Betamethasone Sodium Phosphate and Drug Combination for Pregnant Women with Preterm Premature Rupture of Membranes

    Recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Czechia

  • Study of antibiotic treatment effectiveness in critically ill patients receiving drug combination therapy

    Not yet recruiting

    1 1 1 1
    Investigated drugs:
    France

Glossary

  • Sulbactam sodium: A medicine used in many trials as part of a combination antibiotic. It is usually included to help another antibiotic work better against bacteria that can resist treatment.
  • Beta-lactamase inhibitor: A drug that blocks bacterial enzymes called beta-lactamases. These enzymes can destroy certain antibiotics. By blocking them, the partner antibiotic can stay active longer.
  • Beta-lactamase: An enzyme made by some bacteria that can break down beta-lactam antibiotics (like penicillins and some cephalosporins), causing antibiotic resistance.
  • Antibiotic resistance: When bacteria change in ways that make an antibiotic less effective. Several trials here focus on resistant bacteria such as multidrug-resistant or carbapenem-resistant Acinetobacter baumannii.
  • Multidrug-resistant (MDR): A term used in the Acinetobacter trials meaning the bacteria are resistant to multiple classes (types) of antibiotics.
  • Carbapenem-resistant Acinetobacter baumannii (CRAB): A type of Acinetobacter infection that is resistant to carbapenems (a strong class of antibiotics). Several ICU-focused trials discuss CRAB treatment strategies.
  • Community-acquired pneumonia (CAP): A lung infection that develops outside of a hospital setting. Trials studied ampicillin/sulbactam (Unasyn-S) for CAP in hospitalized or adult patients.
  • Hospital-acquired bacterial pneumonia (HABP): Pneumonia that develops during a hospital stay. Some trials studied sulbactam-based regimens against Acinetobacter-associated HABP.
  • Ventilator-associated bacterial pneumonia (VABP): Pneumonia that occurs in patients using a breathing machine (ventilator). This was included in studies of sulbactam-durlobactam (ETX2514) regimens.
  • Bacteremia: Bacteria present in the bloodstream, usually confirmed by a positive blood culture. Some Acinetobacter trials included bacteremia as a study condition.
  • Peritonitis: Infection or inflammation of the lining inside the abdomen (the peritoneum). High-dose ampicillin/sulbactam surveillance in Japan included peritonitis.
  • Intra-abdominal infection: An infection inside the belly (abdomen), such as localized peritonitis or abscess. Multiple trials compared antibiotics including ampicillin/sulbactam for these infections.
  • Complicated urinary tract infection (cUTI): A urinary tract infection that is harder to treat because of patient factors or infection severity. A double-blind trial studied sulbactam-ETX2514 plus background imipenem/cilastatin in cUTI.
  • Acute pyelonephritis: A kidney infection, often more severe than a simple bladder infection. It was included in cUTI trials and other antibiotic-comparison studies.
  • Bacterial eradication / bacterial clearance: A lab-based outcome showing that the bacteria are no longer detected in cultures from the infection site after treatment.
  • Test of Cure (TOC): A planned follow-up visit after treatment ends to confirm whether the infection is cured, often using symptoms plus lab cultures.
  • Adverse event (AE): Any unwanted medical problem that happens during a study, whether or not it is caused by the drug.
  • Serious adverse event (SAE): A severe side effect that can include death, life-threatening illness, hospital admission or longer hospital stay, disability, or birth defect (as defined in the phase 1 sulbactam/ETX2514 studies).
  • Coagulation disorder: A problem with blood clotting. One study investigated risk factors for drug-induced coagulation dysfunction associated with cefoperazone/sulbactam, using clotting tests such as PT, APTT, TT, and platelet counts.
  • Prothrombin time (PT): A blood test that measures how quickly blood clots through one main clotting pathway. It was used in the coagulation-disorder study.
  • Activated partial thromboplastin time (APTT): A blood test that measures another clotting pathway. It was monitored in the coagulation-disorder study.
  • Thrombin time (TT): A blood test measuring the last step of clot formation (how fibrin forms). It was monitored in the coagulation-disorder study.
  • Platelets (PLT): Blood cells that help stop bleeding by forming clots. Platelet counts were tracked in the coagulation-disorder study.
  • Pharmacokinetics (PK): How the body absorbs, distributes, and removes a drug. PK studies here measured sulbactam levels in blood and sometimes lung compartments.
  • Cmax: The highest (peak) drug concentration measured in blood after dosing. Several PK and bioequivalence trials used Cmax.
  • AUC (Area Under the Curve): A measure of total drug exposure over time (how much drug the body sees). Bioequivalence and PK trials measured AUC values.
  • Bioequivalence: A study approach testing whether two drug products give similar drug levels in the body (for example, Burotam vs Brosym cefoperazone/sulbactam).
  • Extended infusion: Giving an IV antibiotic slowly over a longer time (for example, 3–4 hours) to keep drug levels effective longer. ICU Acinetobacter regimens used extended infusion.
  • Bronchoalveolar lavage (BAL): A procedure during bronchoscopy where sterile fluid is put into a small part of the lung and then collected for testing. One phase 1 study used BAL to measure sulbactam levels in lung fluid and cells.
  • Epithelial lining fluid (ELF): A thin layer of fluid lining the airways where lung infections happen. One phase 1 study measured sulbactam concentrations in ELF.
  • Alveolar macrophages (AM): Immune cells in the lungs that can swallow germs. One study measured sulbactam levels inside these cells.
  • SOFA score: Sequential Organ Failure Assessment score. A scoring system used in ICU patients to track how well major organs are working; higher scores suggest worse organ failure.
  • RIFLE criteria: A system to classify kidney injury severity (Risk, Injury, Failure, Loss, End-stage kidney disease). It was used to evaluate nephrotoxicity in an Acinetobacter pneumonia/bacteremia study and renal failure outcomes in another.
  • Surgical site infection (SSI): An infection that happens at or near the surgery incision or inside the operated area. Several trials studied whether ampicillin/sulbactam prophylaxis reduced SSI after procedures like cesarean section or cholecystectomy.
  • Antibiotic prophylaxis: Using antibiotics to prevent an infection (not to treat an existing infection), such as giving ampicillin/sulbactam before surgery.
  • Presepsin: A blood biomarker studied to help predict or detect infection and sepsis. One cardiac surgery trial used presepsin levels to decide when to switch to ampicillin/sulbactam.
  • Procalcitonin: A biomarker that can rise with bacterial infection. It was measured in a trial related to infections after cardiac device implantation.
  • Interleukin-6 (IL-6): A biomarker of inflammation that can increase during infection. It was measured in the cardiac device prophylaxis trial.

References

  1. https://clinicaltrials.gov/study/NCT01189487
  2. https://clinicaltrials.gov/study/NCT01793688
  3. https://clinicaltrials.gov/study/NCT04202068
  4. https://clinicaltrials.gov/study/NCT03894046
  5. https://clinicaltrials.gov/study/NCT03445195
  6. https://clinicaltrials.gov/study/NCT01760109
  7. https://clinicaltrials.gov/study/NCT04066621
  8. https://clinicaltrials.gov/study/NCT07118384
  9. https://clinicaltrials.gov/study/NCT02688322
  10. https://clinicaltrials.gov/study/NCT00137007
  11. https://clinicaltrials.gov/study/NCT00952796
  12. https://clinicaltrials.gov/study/NCT00630513
  13. https://clinicaltrials.gov/study/NCT00463762
  14. https://clinicaltrials.gov/study/NCT00368537
  15. https://clinicaltrials.gov/study/NCT03303924
  16. https://clinicaltrials.gov/study/NCT05535309
  17. https://clinicaltrials.gov/study/NCT05654090
  18. https://clinicaltrials.gov/study/NCT01888822
  19. https://clinicaltrials.gov/study/NCT01138852
  20. https://clinicaltrials.gov/study/NCT06448624
  21. https://clinicaltrials.gov/study/NCT04290104
  22. https://clinicaltrials.gov/study/NCT06048692
  23. https://clinicaltrials.gov/study/NCT06801223
  24. https://clinicaltrials.gov/study/NCT06440304
  25. https://clinicaltrials.gov/study/NCT05922124