Treatment of amoebic liver abscess with metronidazole alone or in combination with ultrasound-guided needle aspiration: a comparative, prospective and randomized study. Needle aspiration in large amoebic liver abscess. Uncomplicated amebic liver abscess: prospective evaluation of percutaneous therapeutic aspiration. Indications for aspiration of amoebic liver abscess. Amoebic liver abscess: ultrasonographic characteristics and results of different therapeutic approaches. Prospective, randomized inpatient study of oral metronidazole versus oral metronidazole and rifampin for treatment of primary episode of Clostridium difficile-associated diarrhea. Single dose cefuroxime/metronidazole versus metronidazole alone in elective colorectal surgery. A randomized, double-blind, placebo-controlled trial of the combined effect of doxycycline hyclate 20-mg tablets and metronidazole 0.75% topical lotion in the treatment of rosacea. Effectiveness of single dose prophylaxis with cefotaxime and metronidazole compared with three doses of cefotaxime alone in elective colorectal surgery. [Perioperative antibiotic prophylaxis in colon surgery. Metronidazole and tobramycin versus metronidazole alone. A prospective randomized study]. Peroperative systemic prophylaxis in colorectal surgery.
Thirty-nine patients with amoebic liver abscess (ALA), admitted to the Central Hospital of Hué (Vietnam), were evaluated in a comparative, prospective and randomized study for the treatment of ALA. Adult patients with an abscess located in the right liver lobe and an abscess diameter of 6 to 10 cm were included. Bacterial abscesses were excluded by microbiological examination of abscess fluid in all patients. Nineteen patients were treated with metronidazole for 10 days alone and 20 patients were punctured under ultrasound guidance with aspiration of abscess fluid in addition to drug administration. The clinical symptoms fever, pain in right upper abdomen and liver tenderness, and the laboratory parameters erythrocyte sedimentation rate, white blood cells, haemoglobin and C-reactive protein and the abscess size were determined on the day of admission and followed during an observation period of 38 days. Improvement of liver tenderness was significantly faster in the aspiration group during the first 3 days (P < 0.001), whereas all the other parameters showed no differences between the two groups. This minor benefit is obviously not sufficient to justify routine needle aspiration and advocates drug treatment alone for uncomplicated amoebic liver abscesses with a diameter up to 10 cm located in the right liver lobe. The role of percutaneous needle aspiration for therapy of uncomplicated, large amoebic liver abscess (ALA) is not defined. Twenty nine patients of ALA with a cavity larger than 5 cm were randomised to two groups: (i) metronidazole 800 mg tid for 10 days combined with needle aspiration (group A, n = 15) and (ii) metronidazole therapy alone (group B, n = 14). Clinical parameters, viz, fever, pain and abdominal tenderness were recorded daily and graded 0 to 3 (in order of increasing severity). A statistically significant benefit was demonstrated in group A for clinical parameters evaluated. Group A patients took less time to become afebrile from the grade 2 level as compared to group B (3.8 +/- 1.7 days and 5.6 +/- 2.2 days respectively; p < 0.05). Reduction in pain intensity and abdominal tenderness from grade 2 to 1 also occurred earlier in group A (0.7 +/- 0.7 days vs 2.9 +/- 0.9 days for pain, P < 0.001 and 1.7 +/- 0.8 days vs 2.9 +/- 1.2 days for abdominal tenderness, p < 0.001). The mean duration of hospitalization was significantly shorter in group A as compared to group B (5.8 +/- 0.8 days vs 7.4 +/- 1.5 days, p < 0.001). Improvement in haematological and biochemical variables was similar in both groups. We conclude that percutaneous therapeutic needle aspiration of uncomplicated, large ALA hastens clinical recovery. The performance of therapeutic aspiration in the treatment of amebic liver abscess, advocated and practiced in many centers, is controversial. Previously, this practice has been evaluated in retrospective analyses. To test the potential benefit of therapeutic aspiration, the authors undertook a prospective randomized trial in 57 patients admitted for suspected amebic liver abscess during a 15-month period. Sixteen patients were excluded from the trial. The remaining 41 patients were randomly included in one of two study groups to receive amebicidal therapy alone or amebicidal therapy coupled with image-guided percutaneous therapeutic aspiration. All patients in the trial recovered. No statistically significant benefit was demonstrated in the aspiration group for the two objective parameters evaluated: length of hospitalization and duration of time to becoming afebrile. Subjective improvement in symptoms after aspiration was greater in the aspiration group at a marginally statistically significant level. These data do not support the adjunctive performance of percutaneous therapeutic aspiration in the treatment of uncomplicated amebic liver abscess. Amebicidals alone were equally efficacious in treating the group studied. A two-part study was undertaken to determine whether aspiration of amoebic liver abscess (ALA) prevents complications. Eighty patients studied prospectively were randomised into aspiration or non-aspiration groups and were treated with metronidazole. Common factors in patients with complicated diseases were determined to formulate and test indications for aspiration. Records of all patients with ALA admitted to King Edward VIII Hospital, Durban, between October 1983 and December 1984 were analysed to test the validity of the criteria derived from the first part of the study. The findings suggest that aspiration influences the course and outcome of ALA and that the criteria are valid although not necessarily complete. This prospective study was carried out on 33 patients with clinically, serologically and ultrasonographically confirmed amoebic liver abscess. All patients were randomly treated with metronidazole and chlorochin or a combination of medicamentous therapy and percutaneous drainage. Ultrasonographic characteristics of amoebic liver abscesses were rotound or oval shape, usually hypoechogenic content with specific dorsal sonic enhancement, and in the majority of cases, location near liver capsule. Shorter duration of amoebic liver abscess resolution time in the group of patients treated with the combined therapy was observed particularly in the first four weeks of the treatment. The authors concluded that percutaneous drainage in combination with medicamentous therapy represents a successful therapeutic approach in the treatment of amoebic liver abscesses. To date, no randomized trial to address the use of adjunctive rifampin in addition to metronidazole for the treatment of Clostridium difficile-associated diarrhea has been reported. Rifampin has excellent in vitro activity against C. difficile and penetrates into cellular materials where the organisms may persist.
                This was a prospective, randomized, single-blinded study of 39 patients that compared therapy with metronidazole alone versus therapy with metronidazole and rifampin for 10 days to treat laboratory-confirmed primary episode C. difficile-associated diarrhea. Twenty patients were randomly assigned to the metronidazole group, and 19 were randomly assigned to the metronidazole and rifampin group. Data were analyzed by intention-to-treat analysis using the 2-tailed Kaplan-Meier method and the log-rank test.
                Adjunctive rifampin treatment for 10 days, compared with treatment with metronidazole alone for 10 days, was associated with a similar median time to symptom improvement (9.0 days vs. 6.5 days; P=.74), a similar median time to first relapse (26 days vs. 16 days; P=.23), a similar proportion of patients with relapse by study day 40 (42% vs. 38%; P=1.0), and a similar proportion of patients experiencing nonfatal adverse events (37% vs. 40%; P=.55). There were a significantly higher number of deaths in the metronidazole and rifampin group, compared with the metronidazole group (6 of 19 patients vs. 1 of 20 patients; P=.04), but there were fewer laboratory-confirmed relapses by study day 40 (2 vs. 4; P=.66).
                We conclude that there is no role for routine rifampin as an adjunct to treatment with metronidazole for hospitalized patients with C. difficile-associated diarrhea. The cure rates for both treatment groups remain unacceptably low, and better treatments are urgently needed. Sixty assessable patients undergoing elective colonic and rectal surgery were randomly allocated to receive prophylaxis with a combination of 1.5 g cefuroxime plus 500 mg metronidazole or 500 mg metronidazole alone as single doses by the intravenous route, given at the beginning of anesthesia. The two groups were matched for age, sex, malignancy, and type of operation. Primary wound infections were observed in one patient (3.7%) in the combination group and six (18.2%) in the group given metronidazole alone. This trend was not statistically significant. Bacteriologic examination of the anastomoses, abdominal walls, and wounds showed significantly more sterile cultures in the combination group, although more aerobic cefuroxime-resistant isolates were seen in this group. There is no evidence that the emergence of resistant strains had any influence on the outcome of patients in the study. It was concluded that an appropriate antibiotic prophylactic regimen for colorectal surgery should be directed against aerobic and anaerobic organisms. Cefuroxime plus metronidazole is an effective regimen for the prevention of postoperative infection. Subantimicrobial doses of doxycycline may improve outcomes in rosacea when combined with topical metronidazole and used as maintenance monotherapy.
                The purpose of this study was to evaluate the safety and efficacy of doxycycline hyclate 20 mg (subantimicrobial dose doxycycline) administered twice daily as an adjunct to metronidazole 0.75% topical lotion in the treatment of rosacea.
                Patients received subantimicrobial doses of doxycycline twice daily plus metronidazole (n = 20) or placebo plus metronidazole (n = 20) for 12 weeks. Subantimicrobial-dose doxycycline or placebo monotherapy continued for 4 weeks. The primary efficacy measure was change from baseline in total inflammatory lesions at weeks 2 and 16.
                Total inflammatory lesions were reduced significantly (P =.048) by week 4 and by all subsequent visits in the subantimicrobial-dose doxycycline/metronidazole group compared with placebo/metronidazole. Changes from baseline increased over time and were maintained during subantimicrobial-dose doxycycline monotherapy.
                Adjunctive use of subantimicrobial dose doxycycline significantly reduced the clinical signs of rosacea compared with metronidazole alone and may be useful maintenance monotherapy. To compare three doses of cefotaxime alone with a single dose of cefotaxime and metronidazole for the prophylaxis of infection after elective colorectal operations.
                Prospective random control trial.
                Hillerød and Frederiksberg Hospitals, Copenhagen, Denmark.
                660 consecutive patients who were to undergo elective colorectal operations during a 48 month period (January 1987-January 1991); 93 (14%) were withdrawn after randomisation leaving 567 for assessment.
                Mechanical bowel preparation, and then either cefotaxime (Claforan) 2 g intravenously at induction of anaestesia and 3 and 9 hours later (n = 280) or a single dose of cefotaxime 2 g plus metronidazole (Flagyl) 1.5 g intravenously at induction of anaestesia (n = 287).
                44 patients in the cefotaxime group developed wound infection (16%) compared with 19 (7%) in the combined group (p < 0.001). In the cefotaxime group 22 of the 241 patients who had an anastomosis developed leaks (9%) compared with 8 of the 239 in the cefotaxime/metronidazole group (3%). There were no differences in the incidence of intra-abdominal abscesses or burst abdomens. The most common organisms isolated from wounds were Escherichia coli and Bacteriodes fragilis.
                One dose of cefotaxime and metronidazole is active against a wide range of organisms and resulted in significantly fewer wound infections than three doses of cefotaxime alone. 97 patients scheduled to undergo elective surgery for colorectal carcinoma were randomized to receive either three doses of intravenous metronidazole-e and tobramycin or three doses of intravenous metronidazole alone. The first dose was given after induction of general anesthesia, the second at 9 p.m. and the third at 6 a.m. the following day. The study was double-blind, with patients in the metronidazol-alone group given a placebo infusion instead of tobramycin. The overall postoperative infection rate was 19.6% with no statistically significant difference between the two groups. It is concluded that the addition of an aminoglycoside does not afford better protection than prophylaxis with metronidazole alone. In an effort to reduce infection rates in elective colorectal surgery to acceptable levels without oral non-absorbable antimicrobials, using only a short course of systemic antimicrobials, 50 patients were studied in a multicentre trial. Each patient received metronidazole for anti-anaerobic coverage. The anti-aerobic coverage consisted of netilmicin, cefuroxime or placebo, administered in a double-blind manner. Five out of 36 evaluable patients had an infection at the operation site. Two patients had peritonitis (one metronidazole-netilmicin and one metronidazole-placebo) and three had a wound abscess in the abdominal wall (all metronidazole-placebo). It is concluded that a short course of peroperative systemic prophylaxis with metronidazole and netilmicin or cefuroxime--without the use of oral non-absorbable antimicrobials--gave acceptable results in the centres studied.
Therapeutic aspiration in addition to metronidazole to hasten clinical or radiologic resolution of uncomplicated amoebic liver abscesses cannot be supported or refuted by the present evidence. The trials lack methodological rigour and adequate sample size to conclude on the presence of effectiveness of adjunctive image-guided aspiration plus metronidazole versus metronidazole alone. Further randomised trials are necessary.