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Liver abscess is purulent collections in the liver parenchyma that result from microbial infection spread to the liver through the biliary tree, hepatic or portal vein and by extension of adjacent infection or as a result of trauma. Liver abscesses are most commonly pyogenic followed by amoebic and rarely tuberculous or fungal in immunocompromised patients. In the developing country amoebic liver abscess is more frequent than the developed country but secondary bacterial infection of amoebic liver abscess and polymicrobial pyogenic liver abscess are also common.
Pyogenic liver abscess is commonly a polymicrobial infection caused by mixed enteric facultative and anaerobic pathogens. The most commonly isolated organisms are Escherichia coli, Klebsiella pneumoniae, Streptococcus constellatus, Streptococcus anginosus, Streptococcus intermedius, Enterococcus and anaerobes, including Bacteroidesfragilis and Fusobacteriumnecrophorum. Amoebic liver abscess most frequently occur following infection with the parasite Entamoeba histolytica.
Liver abscess is a common medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage of the abscess is therapeutic.
An empiric antimicrobial regimen for liver abscess should cover enteric gram-negative bacilli, streptococci, anaerobes and antamoebahistolytica. Presently a Fluoroquinolone (Ciprofloxacin, Levofloxacin) or a Third or Fourth generation Cefalosporine (Cefixime, Ceftriaxone, cefepime) or a Beta-lactam-beta-lactamase inhibitor combination (piperacillin-tazobactam or ticarcillin-clavulanate) or a Carbapenem (Imipenem-cilastatin, Meropenem, Doripenem, Ertapenem) are being used in combination with or without Metronidazole as the empirical antimicrobial regime for the treatment live abscess. There is no randomized controlled clinical trial to evaluated and compare efficacy of the antimicrobial regimens for the treatment of liver abscess as well as there is no specific treatment guideline for the use of empirical antibiotics. There is also no definite proven rational for using Cefalosporine, Beta-lactam-beta-lactamase inhibitor combination or Carbapenem upfront, not using Fluoroquinolone in empirical antibiotic regimen for the treatment of liver abscess. Injudicious use of broader spectrum antibiotics may also lead to rise in antibiotic resistance in future.
Both ciprofloxacin and Cefixime are effective oral antibiotics as they are well-absorbed orally with good oral bioavailability and achieve plasma concentration well above the minimal inhibitory concentrations require for the killing of the microorganism. Using intravenous (IV) antibiotics upfront, for the treatment of liver abscess in patients who can take orally may unnecessary increase the duration of hospital stay, healthcare burden and the cost of therapy, as well as the risk of hospital acquired infection.
So the investigators have planned this randomized controlled double blind study to evaluate the efficacy of empirical Ciprofloxacin plus Metronidazole and Cefixime plus Metronidazole therapy for the treatment of liver abscess and to compare the outcomes of two different empirical antibiotics regimen.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ciprofloxacin plus Metronidazole therapy | Active Comparator | Will receive tablet Ciprofloxacin (500 mg BDS) and tablet Metronidazole (800 mg TDS) orally for 2 weeks. Percutaneous aspiration or drainage of the liver abscess will be done for all the participants when there is enough liquid content/pus which is amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively. After 2 weeks of empirical antibiotic therapy, asymptomatic patients with persistent drainage with USG showing significant drainable collection in the liver will receive another 2 weeks of extended antimicrobial therapy of same combination. |
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| Cefixime plus Metronidazole Therapy | Active Comparator | Will receive tablet Cefixime (200 mg BDS) and tablet Metronidazole (800 mg TDS) orally for 2 weeks.Percutaneous aspiration or drainage of the liver abscess will be done for all the participants when there is enough liquid content/pus which is amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively. After 2 weeks of empirical antibiotic therapy, asymptomatic patients with persistent drainage with USG showing significant drainable collection in the liver will receive another 2 weeks of extended antimicrobial therapy of same combination. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ciprofloxacin | Drug | will receive tablet Ciprofloxacin (500 mg BDS) and tablet Metronidazole (800 mg TDS) for 2 weeks orally. Percutaneous aspiration or drainage of the liver abscess will be done when there is enough liquid content/pus amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical cure | Asymptomatic and afebrile for more than 48 hours, along with USG showing no drainable collection in the liver with removal of the pigtail catheter if any | 2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment failure | Defined as any one of the following condition
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Deba P Dhibar, MD | Contact | +91722756670 | drdeba_prasad@yahoo.co.in |
| Name | Affiliation | Role |
|---|---|---|
| Deba P Dhibar, MD | PGIMER, Chandigarh, India | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Post Graduate Institute of Medical Education and Research | Chandigarh | 160012 | India |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38769330 | Derived | Priya G L, Dhibar DP, Saroch A, Sharma N, Sharma V, Verma N, Chaluvashetty SB, Prakash A, Kaur H. Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial. Sci Rep. 2024 May 20;14(1):11430. doi: 10.1038/s41598-024-59607-1. |
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There is no plan to share IPD with other researchers except for those are directly involved with this study.
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| ID | Term |
|---|---|
| D008100 | Liver Abscess |
| ID | Term |
|---|---|
| D018784 | Abdominal Abscess |
| D000038 | Abscess |
| D013492 | Suppuration |
| D007239 | Infections |
| D008107 |
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| ID | Term |
|---|---|
| D002939 | Ciprofloxacin |
| D008795 | Metronidazole |
| D020682 | Cefixime |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
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Double Blind
|
|
| Cefixime | Drug | will receive tablet Cefixime (200 mg BDS) and tablet Metronidazole (800 mg TDS) for 2 weeks orally. Percutaneous aspiration or drainage of the liver abscess will be done when there is enough liquid content/pus amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and <5 cm respectively. |
|
|
| 8 weeks |
| All-cause mortality | Total number of death | 8 weeks |
| Recurrence of liver abscess | Development new liver abscess after clinical cure during the 8 weeks follow up period | 8 weeks |
| Need for surgical intervention | number of patients needing surgical intervention for the treatment of liver abscess | 8 weeks |
| Need for mechanical ventilation | Number of patients needing mechanical ventilation for the respiratory failure. | 8 weeks |
| Need for prolong antibiotics 11. | Number of asymptomatic patients receiving 2 weeks of extended antibiotic therapy due to persistent drainage or aspiration even after 2 weeks of empirical antibiotics | 8 weeks |
| Duration of hospital stay | Number of days of hospital stay for the treatment of liver abscess | 8 weeks |
| Adverse drug events (ADE) | Number of adverse drug events | 8 weeks |
| Localised bio-availability of the drugs (Ciprofloxacin, Metronidazole and Cefixime) | Concentration of the drug in drained pus/Concentration of drug in the serum X100 on the day-three of the drainage (when applicable) | 8 weeks |
| Liver Diseases |
| D004066 | Digestive System Diseases |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009593 | Nitroimidazoles |
| D009574 | Nitro Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D002439 | Cefotaxime |
| D002505 | Cephacetrile |
| D002511 | Cephalosporins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D013843 | Thiazines |
| D013457 | Sulfur Compounds |