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Antibiotic time-lag combination therapy with fosfomycin for postoperative intra-abdominal abscesses
Shinya Kusachi1, Jiro Nagao, Yoshihisa Saida
1Department of Surgery, Toho University Medical Center Ohashi Hospital, Tokyo, Japan. kusachi@med.toho-u.ac.jp
Abstract:
The first-line treatment for intra-abdominal abscess is source control. Sometimes, however, source control is too invasive for relatively small abscesses and is not feasible due to the risk of injury to some organs. Based on reports that fosfomycin (FOM) can break up biofilms to enhance the permeability of other antibiotics, we investigated the FOM time-lag combination therapy (FOM-TLCT). We enrolled 114 patients who had intra-abdominal abscess after gastrointestinal surgery and examined the efficacy of FOM-TLCT using the same therapeutic antibiotic (TA) as that which had been used previously, but had proven ineffective, at the same dose schedule. The efficacy endpoint determination was carried out as follows: among the systemic inflammatory response syndrome (SIRS)-positive cases, even after administration of TA, excellent outcome was defined as SIRS negative within 7 days of FOM-TLCT with TA without the need for other treatment, including other antibiotics or drainage. Of the 114 patients enrolled, 104 cases (SIRS positive 73; SIRS negative 31) were assessed. Ten patients were excluded; four had received TA at higher doses, three had received different TAs, and three were considered to have bacteria resistant to TAs. Among these patients, 86.3% (63/73) of the SIRS-positive cases were classified as excellent, and 90.3% (28/31) of the SIRS-negative cases were classified as effective. In total, the efficacy rate was 87.5% (91/104). The total no-response rates were 12.5% (13/104). FOM-TLCT seems to be effective for treating refractory intra-abdominal abscess.
Insights
Fosfomycin (FOM) time-lag combination therapy (FOM-TLCT) offers a promising treatment for difficult intra-abdominal abscesses. This approach enhances existing antibiotic effectiveness, showing high success rates in patients unresponsive to standard therapies.
Area of Science:
- Infectious Diseases
- Surgical Infections
- Pharmacology
Background:
- Intra-abdominal abscess treatment typically relies on source control, which can be too invasive for smaller abscesses.
- Alternative therapies are needed when source control is not feasible or carries significant risks.
Purpose of the Study:
- To investigate the efficacy of fosfomycin (FOM) time-lag combination therapy (FOM-TLCT) for refractory intra-abdominal abscesses.
- To evaluate if FOM can enhance the efficacy of previously ineffective therapeutic antibiotics (TA).
Main Methods:
- 114 patients with post-gastrointestinal surgery intra-abdominal abscesses were enrolled.
- FOM-TLCT was administered using the patient's prior ineffective TA at the same dosage.
- Efficacy was assessed by resolution of systemic inflammatory response syndrome (SIRS) within 7 days.
Main Results:
- Of 104 assessed patients, 87.5% (91/104) showed an effective response.
- Excellent outcomes (SIRS negative within 7 days without further intervention) were achieved in 86.3% (63/73) of SIRS-positive cases.
- Effective outcomes were observed in 90.3% (28/31) of SIRS-negative cases, with a 12.5% no-response rate.
Conclusions:
- FOM-TLCT demonstrates significant efficacy in treating refractory intra-abdominal abscesses.
- This combination therapy provides a viable alternative when standard treatments fail.
- Further research into FOM's role in biofilm disruption and antibiotic synergy is warranted.
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