Inflammation-Induced Attenuation of Prostaglandin D2 Elimination across Rat Blood-Brain Barrier: Involvement of the Downregulation of Organic Anion Transporter 3 and Multidrug Resistance-Associated Protein 4.

Prostaglandin (PG) D2 is a lipid mediator, and in the brain, overproduction of PGD2 is reportedly involved in the progression and exacerbation of neuroinflammation. The objective of this study was to elucidate PGD2 efflux transport, under normal and inflammatory conditions, across the blood-brain barrier (BBB), which is formed by brain capillaries. Elimination of [3H]PGD2 across the BBB of normal and lipopolysaccharide (LPS)-induced inflammatory rats was examined by the intracerebral microinjection technique. After intracerebral injection, the percentage of [3H]PGD2 remaining in the ipsilateral cerebrum decreased with time, with a half-life of 13 min. This [3H]PGD2 elimination across the BBB was significantly inhibited by the co-administration of unlabeled PGD2, which suggests carrier-mediated PGD2 efflux transport at the BBB. In isolated rat brain capillaries, mRNA expression of organic anion transporter (Oat) 3, organic anion-transporting polypeptide (Oatp) 1a4, and multidrug resistance-associated protein (Mrp) 4 was observed. In addition, co-administration of substrates/inhibitors for Oat3, Oatp1a4, and/or Mrp4, such as benzylpenicillin and cefmetazole, reduced [3H]PGD2 elimination across the BBB. Data suggest that Oat3 and Mrp4, but not Oatp1a4 are involved in PGD2 elimination across the BBB, as Oatp1a4-expressing Xenopus (X.) oocytes did not show the significant [3H]PGD2 uptake compared with water-injected X. oocytes. In LPS-treated rats, [3H]PGD2 elimination across the BBB and mRNA expression levels of Oat3 and Mrp4 were significantly decreased. Our data suggest that Oat3- and Mrp4-mediated PGD2 elimination across the BBB is attenuated under inflammatory conditions.

Preoperative mechanical bowel preparation with oral antibiotics reduces surgical site infection after elective colorectal surgery for malignancies: results of a propensity matching analysis.

BACKGROUND: Surgical site infections (SSIs) are a major postoperative complication after colorectal surgery. Current study aims to evaluate prophylactic function of oral antibiotic (OA) intake in combination with mechanical bowel preparation (MBP) relative to MBP alone with respect to postoperative SSI incidence. METHODS: A retrospective analysis of eligible patients was conducted using the databases of the Gastrointestinal Surgery Centre, Third Affiliated Hospital of Sun Yat-sen University from 2011 to 2017. Data pertaining to postoperative hospital stay length, expenses, SSI incidence, anastomotic fistula incidence, and rates of other complications were extracted and compared. A propensity analysis was conducted to minimize bias associated with demographic characteristics. Subgroup analyses were performed to further explore protective effects of OA in different surgical sites. RESULTS: The combination of OAs and MBP was related to a significant decrease in the incidence of overall SSIs, superficial SSI, and hospitalization expenses. The MBP + OA modality was particularly beneficial for patients undergoing left-side colon or rectum resections, with clear prophylactic efficacy. The combination of MPB + OA did not exhibit significant prophylactic efficacy in patients undergoing right hemi-colon resection. Age, surgical duration, and application of OA were all independent factors associated with the occurrence of SSIs. CONCLUSION: These results suggest that the combination of OA + MBP should be recommended for patients undergoing elective colorectal surgery, particularly for operations on the left side of the colon or rectum. TRIAL REGISTRATION: NCT04258098. Retrospectively registered.

One-day versus four-day antibiotic treatment for acute right colonic uncomplicated diverticulitis: A randomized clinical trial.

BACKGROUND/AIMS: Currently, right colonic uncomplicated diverticulitis is typically treated with antibiotic therapy. However, the optimal duration of treatment is unknown. The aim of the present study was to compare the treatment failure rates between 1- and 4-day antibiotic treatment protocols. MATERIALS AND METHODS: A prospective randomized study in adults presenting with uncomplicated diverticulitis at the first episode from July 2011 to June 2014 was performed. Patients were randomized to receive intravenous antibiotics for 1 day (1-day group) or intravenous and oral antibiotics for 4 days (4-day group). All patients received cefmetazole and metronidazole. Treatment failure was defined as readmission within 30 days and disease recurrence during the follow-up period. RESULTS: Overall, 87 and 89 patients were randomized to the 1-day and 4-day groups, respectively. All patients were successfully treated initially. The hospital length of stay was shorter in the 1-day group than in the 4-day group (3.1 vs. 3.8 days, respectively; p<0.001). After discharge, there were no significant differences between the groups in treatment failure (15/87, 17.2% vs. 19/89, 21.3%; p=0.493). In each group, there were readmission within 30 days (9.2% vs. 12.4%; p=0.502) and recurrence over a median follow-up period of 32 months (10.3% vs. 9.0%; p=0.762). In 34 patients who experienced treatment failure, 6 required surgery. CONCLUSION: Single-day antibiotic treatment is as effective as 4-day therapy for the prevention of readmission and recurrence in patients with right colonic uncomplicated diverticulitis.

The use of broad-spectrum antibiotics reduces the incidence of surgical site infection after pancreatoduodenectomy.

PURPOSE: The development of surgical site infection (SSI) after biliary reconstruction is highly influenced by the presence of preoperative bacteria in the bile juice. We selected vancomycin and piperacillin/tazobactam (VCM + PIPC/TAZ) as perioperative prophylactic antibiotics for patients undergoing pancreaticoduodenectomy. This study aimed to retrospectively analyze the effectiveness of VCM + PIPC/TAZ compared to cefmetazole. METHODS: Seventy-two patients who underwent pancreaticoduodenectomy between April 2015 and March 2017 at our department were evaluated. Forty patients were administered cefmetazole as the perioperative prophylactic antibiotic, and 32 were administered VCM + PIPC/TAZ. The intraoperative VCM blood concentration (incision, biliary reconstruction, and wound closure) was measured during surgery to confirm the hemodynamics. RESULTS: The frequency of SSIs was significantly lower in the VCM + PIPC/TAZ group (8/32 patients) than in the cefmetazole group (20/40 patients, P = 0.031). Postoperatively, significantly fewer patients in the VCM + PIPC/TAZ group (4/32 patients) required ≥ 15 days of additional antibiotic administration compared to those in the cefmetazole group (14/40 patients, P = 0.033). Six of 32 patients in the VCM + PIPC/TAZ group showed redneck syndrome symptoms. There was no significant difference in the VCM blood concentration between patients with and without SSIs. CONCLUSIONS: The use of VCM + PIPC/TAZ can reduce the incidence of SSI after pancreaticoduodenectomy and also reduce the need for the additional administration of antibiotics for ≥ 15 days after surgery.

Total bilirubin amount in drainage fluid can be an early predictor for severe biliary fistula after hepatobiliary surgery.

The ratio of the bilirubin concentration in abdominal drainage fluid to the serum bilirubin concentration (d-Bil/s-Bil) has been used as a predictor of biliary fistula (BF) formation after hepatobiliary surgery. The d-Bil/s-Bil ratio is highly influenced by the amount of drainage and is not always reliable, especially when the amount of drainage is large. In this study, the usefulness of the d-Bil/s-Bil ratio and total bilirubin amount in the drainage fluid (TBA) (bilirubin concentration in the drainage fluid x the amount of drainage) as predictors of severe BF (sBF) formation was evaluated retrospectively from the data of 306 patients who had undergone hepatobiliary surgery. Of the 306 patients, 201 patients were included in the training set and the remaining 105 in the validation set, to determine the best parameter to predict sBF formation after hepatobiliary surgery. Receiver-operating characteristic curve analysis revealed that the predictive power of TBA was superior to that of the d-Bil/s-Bil ratio throughout the postoperative period, and that the TBA on postoperative day (POD) 1 showed the highest discriminatory power in the training set (area under the curve, 0.789; cutoff value, 470 mg/day). The TBA on POD 1 also showed the highest predictive power for sBF formation in the validation set, with a sensitivity of 100%, specificity of 97.1%, and accuracy of 97.1%. In conclusion, TBA may be a more reliable predictor of sBF than the conventionally used d-Bil/s-Bil ratio. Early prediction of sBF may be useful for early removal of unnecessary prophylactic drainage tubes after hepatobiliary surgery.

Predicting postoperative fever and bacterial colonization on packing material following endoscopic endonasal surgery.

Postoperative fever following endoscopic endonasal surgery is a rare occurrence of concern to surgeons. To elucidate preoperative and operative predictors of postoperative fever, we analyzed the characteristics of patients and their perioperative background in association with postoperative fever. A retrospective review of 371 patients who had undergone endoscopic endonasal surgery was conducted. Predictors, including intake of antibiotics, steroids, history of asthma, preoperative nasal bacterial culture, duration of operation, duration of packing and intraoperative intravenous antibiotics on the occurrence of postoperative fever, and bacterial colonization on the packing material, were analyzed retrospectively. Fever (≥38 °C) occurred in 63 (17 %) patients. Most incidences of fever occurred on postoperative day one. In majority of these cases, the fever subsided after removal of the packing material without further antibiotic administration. However, one patient who experienced persistent fever after the removal of packing material developed meningitis. History of asthma, prolonged operation time (≥108 min), and intravenous cefazolin administration instead of cefmetazole were associated with postoperative fever. Odds ratios (ORs) for each were 2.3, 4.6, and 2.0, respectively. Positive preoperative bacterial colonization was associated with postoperative bacterial colonization on the packing material (OR 2.3). Postoperative fever subsided in most patients after removal of the packing material. When this postoperative fever persists, its underlying cause should be examined.

Randomized clinical trial of oral and intravenous versus intravenous antibiotic prophylaxis for laparoscopic colorectal resection.

BACKGROUND: The use of oral prophylactic antibiotics for the prevention of surgical-site infection (SSI) in patients undergoing laparoscopic surgery for colorectal cancer is controversial. The aim of this RCT was to evaluate whether intravenous perioperative antibiotics are inferior to combined preoperative oral and perioperative intravenous antibiotics in this setting. METHODS: Patients undergoing elective laparoscopic colorectal resection in a single cancer centre were assigned randomly to combined preoperative oral antibiotics (metronidazole and kanamycin) and perioperative intravenous antibiotics (cefmetazole) (oral/IV group) or to perioperative intravenous antibiotics (cefmetazole) alone (IV-only group). Patients were stratified for the analyses based on type of operation (colonic surgery, anterior resection or abdominoperineal resection), preoperative use of mechanical bowel preparation, preoperative chemoradiotherapy and the presence of diabetes mellitus. The primary endpoint was the overall rate of SSI. Secondary endpoints were the rates of incisional site infection, organ/space infection, anastomotic leakage, intra-abdominal abscess, adverse events and postoperative complications. RESULTS: Of 540 patients offered participation in the trial in 2013-2014, 515 agreed to take part and were randomized. Some 256 patients in the IV-only group and 255 in the oral/IV group completed the treatment per protocol. The overall rate of SSI was 7·8 per cent (20 of 256) in the IV-only group and 7·8 per cent (20 of 255) in the oral/IV group, confirming that perioperative administration of intravenous antibiotics alone was not inferior to the combined regimen (P = 0·017). There were no differences in rates of incisional site infection (5·5 versus 5·9 per cent respectively), organ/space infection (2·3 versus 2·0 per cent) or other secondary endpoints between the two groups. CONCLUSION: Intravenous perioperative antimicrobial prophylaxis alone is not inferior to combined preoperative oral and intravenous perioperative prophylaxis with regard to SSI in patients with colorectal cancer undergoing elective laparoscopic resection. Registration number: UMIN000019339 ( http://www.umin.ac.jp/ctr/).

Oral and Parenteral Versus Parenteral Antibiotic Prophylaxis in Elective Laparoscopic Colorectal Surgery (JMTO PREV 07-01): A Phase 3, Multicenter, Open-label, Randomized Trial.

OBJECTIVE: To confirm the efficacy of oral and parenteral antibiotic prophylaxis (ABX) in the elective laparoscopic colorectal surgery. BACKGROUND: There is no evidence for the establishment of an optimal ABX regimen for laparoscopic colorectal surgery, which has become an important choice for the colorectal cancer patients. METHODS: The colorectal cancer patients scheduled to undergo laparoscopic surgery were eligible for this multicenter, open-label, randomized trial. They were randomized to receive either oral and parenteral prophylaxis (1 g cefmetazole before and every 3 h during the surgery plus 1 g oral kanamycin and 750 mg metronidazole twice on the day before the surgery; Oral-IV group) or parenteral prophylaxis alone (the same IV regimen; IV group). The primary endpoint was the incidence of surgical site infections (SSIs). Secondary endpoints were the incidence rates of Clostridium difficile colitis, other infections, and postoperative noninfectious complications, as well as the frequency of isolating specific organisms. RESULTS: Between November 2007 and December 2012, 579 patients (289 in the Oral-IV group and 290 in IV group) were evaluated for this study. The incidence of SSIs was 7.26% (21/289) in the Oral-IV group and 12.8% (37/290) in the IV group with an odds ratio of 0.536 (95% CI, 0.305-0.940; P = 0.028). The 2 groups had similar incidence rates of C difficile colitis (1/289 vs 3/290), other infections (6/289 vs 5/290), and postoperative noninfectious complications (11/289 vs 12/290). CONCLUSIONS: Our oral-parenteral ABX regimen significantly reduced the risk of SSIs following elective laparoscopic colorectal surgery.

Serum concentrations of antibiotics during severe invasive surgery such as esophagectomy for esophageal cancer.

This study was performed to confirm the antibiotic regimen during a severe invasive surgery, such as esophagectomy, with a long procedure and a large amount of normal volumes of infusion. Ten patients with esophageal cancer were enrolled in this study, and cefmetazole sodium concentrations in serum were measured during esophagectomy. The ranges of minimum inhibitory concentrations for 90% of isolates of cefmetazole sodium for microorganisms in our institutions for 8 years were investigated. The maximum concentration was 83.9 µg/mL just after the completion of infusion, and its half-life was 1.5 hours. Serum concentration of cefmetazole sodium was kept above 16 µg/mL for 4 hours during esophagectomy. It was kept above 32 µg/mL for 2.5 hours after injection. There are almost no differences in the pharmacokinetics of cefmetazole sodium between common use and during esophagectomy. In addition, additive infusion of antibiotics 4 hours after the first infusion was recommended during esophagectomy.

Effectiveness of multimodal pain management after bipolar hemiarthroplasty for hip fracture: a randomized, controlled study.

BACKGROUND: Appropriate pain management affects outcome after hip fracture surgery. Although multimodal pain management is commonly used for pain control for patients undergoing elective surgery, few studies have evaluated its use in those undergoing hip fracture surgery. This prospective randomized study was designed to determine the clinical value of multimodal pain management with preemptive pain medication and intraoperative periarticular multimodal drug injections in patients undergoing bipolar hip hemiarthroplasty. METHODS: Of eighty-two cognitively intact elderly patients about to undergo bipolar hemiarthroplasty after a hip fracture, forty-three were randomly assigned to receive preemptive pain medication and intraoperative periarticular injections (Group I) and thirty-nine were assigned to not receive preemptive medication and injections (Group II). These two groups were compared with regard to the pain level on postoperative days one, four, and seven; at discharge; and when they started walking and standing exercises. Total amounts of fentanyl used, the frequency of use of patient-controlled analgesia, patient satisfaction at discharge, and perioperative complications were recorded. RESULTS: Group I had a lower pain level than Group II on postoperative days one and four, but no intergroup difference in pain level was observed on postoperative day seven. The total amount of fentanyl used and the frequency of use of patient-controlled analgesia were also lower in Group I. Patient satisfaction at discharge was higher in Group I. No significant intergroup differences were found in the times until the patients walked or performed standing exercises or in the complications. CONCLUSIONS: Multimodal pain management provides additional pain relief until the fourth postoperative day, improves patient satisfaction at discharge, and reduces total narcotic consumption for postoperative pain management after hip hemiarthroplasty for hip fractures.

The efficacy of cefmetazole against pyelonephritis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae.

OBJECTIVES: Urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are on the increase. Although cefmetazole is stable in vitro against the hydrolyzing activity of ESBLs, no clinical study has ever evaluated its role in infections caused by these organisms. We therefore evaluated the efficacy of cefmetazole compared to carbapenems against pyelonephritis caused by ESBL-producing Enterobacteriaceae. METHODS: A retrospective chart review was conducted at a tertiary care hospital from August 2008 to July 2010. Chart reviews were done for patients with ESBL-producing organisms in urine identified in the microbiology database. Patients who were treated with cefmetazole were compared to those treated with carbapenems. The clinical and bacteriological cure rates at 4 weeks after completion of therapy were evaluated. RESULTS: Two hundred and fifty-six urine cultures growing ESBL-producing organisms were identified during the study period. Ten patients treated with cefmetazole and 12 patients treated with carbapenems were evaluated. There was no difference in clinical (9/10 vs. 12/12, p = 0.46) or bacteriological cure rate (5/7 vs. 6/7, p = 1.00) at 4 weeks after the completion of therapy. There was no difference in the incidence of adverse effects (2/10 vs. 2/12, p = 1.00). CONCLUSIONS: Cefmetazole may be a useful option for the treatment of UTIs caused by ESBL-producing organisms. Prospective and larger sized studies are needed to confirm our findings.

Characterization of chitosan-carboxymethyl dextran nanoparticles as a drug carrier and as a stimulator of mouse splenocytes.

The in vitro drug-release behavior of chitosan-carboxymethyl dextran nanoparticles (CDNP) containing cefmetazole, 5-fluorouracil (5-FU) or indocyanine green (ICG), and the in vitro effect of CDNP on mouse B16 melanoma cell proliferation and in vivo modulation effect of CDNP on serum cytokines and spleen lymphocytes in mice were evaluated in this study. Drug-loaded CDNP were prepared by embedding (for cefmetazole or 5-FU) and absorption (for ICG), and the particle size was increased with increased drug association efficiency (AE) and decreased surface amino group content. Prolonged release of cefmetazole (540 min) or 5-FU (360 min) from CDNP was observed when compared to that of nanoparticle-free cefmetazole (210 min) or 5-FU (50 min), and the release of cefmetazole or 5-FU from CDNP98 (CDNP made with 98% degree of deacetylation (DD) chitosan) was slower than from CDNP78 (CDNP made with 78% DD chitosan). High AE (72.0-98.6%), undetectable surface amino group content and dramatically increased particle size (1076.9-1506.0 nm) of ICG-loaded CDNP with undetectable release of ICG within 48 h revealed the good affinity between ICG and CDNP. Twenty-five to 100 µg/ml of CDNP elicited dose-dependent inhibitory effects on B16 tumor cell proliferation, and CDNP98 was more effective than CDNP78. CDNP78 regulated serum IL-17 level in up-regulating IL-4, IL-6, IL-10, IL-23 and TGF-ß within 3 h; on the other hand, CDNP98 significantly down-regulated TGF-ß and had no induction effect on IL-23 within 24 h. In addition, reduced IL-17 was observed in CDNP at 24 h. CDNP98 was more effective than CDNP78 in stimulating mouse splenic T CD4(+), TCD8(+) and NK cell proliferation within 24 h, while CDNP78 was superior to CDNP98 in stimulating B CD19(+) cells. The ability of CDNP to be the drug carrier and to enhance both humoral and cell-mediated immune response in this study demonstrated its promising potential to be applied as biomedical material.

Multicenter prospective randomized phase II study of antimicrobial prophylaxis in low-risk patients undergoing colon surgery.

PURPOSE: Postoperative antimicrobial therapy is generally administered as standard prophylaxis against postoperative infection, despite a lack of sufficient evidence for its usefulness. This study was a phase II study to evaluate the necessity of postoperative antibiotic prophylaxis in patients undergoing a colectomy. METHODS: Patients received 1 g cefmetazole or flomoxef immediately after anesthetic induction, every 3 h during surgery, and then later once again on the next day. They were randomly assigned to receive either cefmetazole or flomoxef. RESULTS: Ninety-one patients were enrolled in the study. A surgical site infection (SSI) occurred in 7.7% (7/91) of patients. All cases were superficial incisional infections. When comparing the two drugs, SSI occurred in 8.3% (4/48) of patients treated with cefmetazole and in 7.0% (3/43) treated with flomoxef, showing no significant difference (P > 0.99). CONCLUSION: Antimicrobial prophylaxis was well tolerated when used on the day of a colectomy and once again on the next day.

Implementing a standard protocol to decrease the incidence of surgical site infections in rectal cancer surgery.

PURPOSE: To evaluate the effectiveness of our surgical site infection (SSI) preventive strategies for rectal cancer patients. METHODS: We compared the incidences and risk factors for SSI before (1990-1999) and after the implementation of our SSI prevention policies (2002-2006). A total of 250 patients who underwent surgery for rectal cancer were enrolled in this study. Peripheral venous blood samples were obtained perioperatively to measure the circulating pro- and anti-inflammatory cytokines. RESULTS: The incidence of SSI was significantly lower after the introduction of SSI prevention policies [SPP(+)] than before [SPP(-)], at 13.1% vs 32.0%, respectively (P = 0.0004). Even with the infection control programs, abdominoperineal resection (APR) was an independent factor predictor of SSI after rectal cancer surgery. The consumption of postoperative interleukin (IL)-6 soluble receptor was much higher in the APR patients than in the non-APR patients. The exaggeration of postoperative IL-6 response was more pronounced in the APR patients in the SPP(+) group than in those in the SPP(-) group, although preoperative chemotherapy and/or radiotherapy might have influenced the inflammatory response. CONCLUSIONS: These findings suggest that the introduction of SPP helped reduce the incidence of SSI, especially in the non-APR patients.

Effects of air tourniquet on the antibiotics concentration, in bone marrow, injected just before the start of operation.

Infection is one of the most serious complications after artificial arthroplasty. In order to establish the effective prevention for after operative infection, we measured the serum and bone marrow blood cefmetazole (CMZ) concentration time dependently (1 g CMZ, one shot). Furthermore, we studied the effect of air tourniquet on CMZ transmit into bone marrow blood. Thirteen knees with total knee arthroplasty (TKA) were included in the study. As a control group, 11 hips with total hip arthroplasty (THA) were also included. In TKA, air tourniquet was used during operation in all cases. Just before the start of the operation, 1 g CMZ was injected intravenously (one shot). Subsequently we sampled peripheral blood and bone marrow blood time dependently. Cefmetazole concentration was measured with HPLC. In the THA group, serum and bone marrow blood CMZ concentration showed almost the same time-dependent change. On the other hand, in the TKA group we could not detect CMZ in bone marrow blood in cases where CMZ was injected within 8 min before starting use of an air tourniquet. If CMZ was injected more than 10 min before starting use of the air tourniquet, CMZ concentration in bone marrow blood was much lower than minimum inhibitory concentration (MIC) for Staphylococcus aureus; but after releasing the air tourniquet, CMZ concentration in bone marrow blood was higher than MIC for S. aureus. These data suggested that our injection method is effective for prevention of infection both during and just after operation in the THA but in the TKA, CMZ should be injected more than 10 min before starting to use the air tourniquet.

Randomized, multicenter trial of antibiotic prophylaxis in elective colorectal surgery: single dose vs 3 doses of a second-generation cephalosporin without metronidazole and oral antibiotics.

HYPOTHESIS: Use of prophylactic antibiotics in elective colorectal surgery is essential. Although single-dose prophylactic antibiotics are recommended, the efficacy of single-dose cephalosporin without metronidazole and oral antibiotics is not fully proven. We conducted a multicenter, randomized trial of a single dose vs 3 doses of the second-generation cephalosporin cefmetazole. DESIGN: A prospective, randomized, multicenter trial in patients undergoing elective colorectal surgery. SETTING: Seven major hospitals in Japan that offer cancer treatment. PATIENTS: Patients with colorectal cancer treated from May 6, 2004, to April 25, 2005. INTERVENTIONS: Patients were randomized to 1 of 2 groups: a single-dose group given a single dose of cefmetazole just before skin incision and a 3-dose group given 2 additional doses of cefmetazole every 8 hours after the first dose just before skin incision. MAIN OUTCOME MEASURES: Incidences of incisional surgical site infection (SSI), organ or space SSI, and all other infectious complications within 30 days after surgery. RESULTS: A total of 384 patients were enrolled. Seven patients were excluded because of additional surgery or the inability to tolerate mechanical preparation. The incidence of incisional SSI was higher in the single-dose group (27/190 or 14.2%) than in the 3-dose group (8/187 or 4.3%) (P = .009). Incidences of organ or space SSI and other postoperative infectious diseases did not differ significantly between the 2 groups. In multivariate analysis, antibiotic dose was the only significant factor related to the incidence of incisional SSI. CONCLUSION: Three-dose cefmetazole administration is significantly more effective for prevention of incisional SSI than single-dose antibiotic administration. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00292708.

[Prophylactic effect of fosfomycin on postoperative infection in gastroenterological surgery].

Fosfomycin (FOM), a drug with unique mechanism of action against bacteria, was prospectively compared with cefmetazole (CMZ) and flomoxef (FMOX) to assess its effectiveness in preventing postoperative infections after upper gastroenterological and hepatobiliary surgery. FOM (2g/dose), CMZ (1 g/dose), or FMOX (lg/dose) was infused intravenously 2-3 times daily for basically 4 days including the day of surgery in order to examine whether or not infections would develop after surgery. According to the analysis results of 162 cases, efficacy in preventing infection was 86.8% for FOM, 73.1% for CMZ and 83.3% for FMOX, showing no significant differences among the 3 groups. Thus FOM was considered as efficacious as CMZ or FMOX in prophylaxis against postoperative infections. There were no adverse reactions in the FOM or CMZ group, but 3 cases of adverse reactions occurred in the FMOX group. Based on the above results, the usefulness of FOM for prophylaxis against postoperative infections has been confirmed. At present, the first- and second-generation cephems are most frequently used for prophylaxis against postoperative infections. In order to prevent an increase of resistant strains due to inappropriate use of these drugs, FOM, having no cross resistance with currently used drugs, is a promising candidate for prophylaxis against postoperative infections.

The significance of the intraoperative repeated dosing of antimicrobials for preventing surgical wound infection in colorectal surgery.

PURPOSE: It is widely accepted that antimicrobial prophylaxis is useful for the prevention of surgical wound infection, especially in colorectal surgery. While many reports support the finding that the first dose should be administered immediately before surgery, there is less evidence concerning the ideal timing for the second dose. The purpose of this study is to examine the significance of intraoperative repeated dosing. METHODS: A surgical series of 131 patients with primary colorectal cancer was retrospectively analyzed for 14 parameters, including the protocols of antimicrobial administration to determine the clinical risk factors for surgical wound infection. RESULTS: The overall surgical wound infection rate of the 131 patients was 16.0% (21/131). When the operation finished within 4 h after the first dose (n = 29), wound infection was observed in only one patient (3.4%). In a prolonged operation exceeding 4 h after the first dose, the surgical wound infection rates were 8.5% and 26.5%, respectively, for those with (n = 47) and without (n = 49) intraoperative repeated dosing, which were significantly different based on both a univariate analysis (P = 0.031) and a multivariate analysis (P = 0.0079). CONCLUSION: Intraoperative repeated antimicrobial dosing is therefore recommended to prevent the surgical wound infection for prolonged colorectal surgery.

[A case of radiofrequency ablation therapy for recurrent hepatomas with tumor fever--efficacy of hepatic arterial infusion therapy with antibiotics and anticancer drugs].

Efficacy of hepatic arterial infusion therapy (HAI) using antibiotics for hepatic abscess has been reported. However, we effectively performed RFA therapy after HAI with antibiotics and anticancer drugs for recurrent hepatomas with tumor fever. A 67-year-old female of recurrent hepatomas with fever is presented here. She was diagnosed with a 6 cm recurrent hepatoma, both in the right and IM lobes. Her liver function was child A with hepatitis C. On her CT scan, we found an enhanced 60 mm mass at an early phase and it was washed out at a delayed phase. Initially, we gave systemic medication of antibiotics, but could not decrease the fever. Therefore, we performed HAI with antibiotics and anticancer drugs. The patient's temperature went down after 14 days, and we were able to cut down her tumor size. After HAI, we were able to completely perform RFA for recurrent hepatomas.

[Successful combination therapy of teicoplanin with cefmetazole on postoperative cardiovascular MRSA infections: clinical report on two cases].

We clinically evaluated the efficacy of the combination therapy of teicoplanin (TEIC) with cefmetazole (CMZ) in two patients, one (case 1) had developed surgical site infection and the other (case 2) mediastinitis caused by methicillin-resistant Staphylococcus aureus (MRSA) after cardiovascular surgeries. TEIC (400 mg twice a day on day-1 and 400 mg once a day thereafter) was administered intravenously immediately after the end of drip infusion of CMZ (1.0 g twice a day). Both patients showed marked improvement on the 5th-day. The isolated MRSA from these two cases were subjected to the in vitro studies and synergistic effects between TEIC and CMZ were recognized under the checkerboard method. Thus, the favorable effects of the combination therapy might be attributable to the synergy between TEIC and CMZ recognized in vitro. These results suggest that the combination therapy of TEIC with CMZ may be useful in the treatment of severe MRSA infections.