Antibiotic treatment for Clostridium difficile-associated diarrhea (CDI) in adults
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01.08.2017 • Sonuncu dəyişiklik 01.08.2017
Editors
In initial symptomatic resolution of mild to moderate C. difficile-associated diarrhoea (CDI), vancomycin may be superior to metronidazole and fidaxomicin may superior to vancomycin. However, the differences in effectiveness between these antibiotics are not large and metronidazole is far cheaper compared to the other two antibiotics.
metronidazole, vancomycin and other antibiotics including fusidic acid, nitazoxanide or rifaximin may be effective Teicoplanin may be slightly more effective but at much greater cost.
A Cochrane review included 22 studies with a total of 3215 subjects.
The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group.
Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. 72% (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. 71% (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. 87% (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46).
One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co-morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co-morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes.
Nine different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin and fidaxomicin (OPT-80). Most of the studies were active comparator studies comparing vancomycin with other antibiotics. Patients with severe CDAD were often excluded from the included studies.
In the only placebo-controlled trial vancomycin was found to be superior to placebo for treatment of CDAD for initial symptomatic cure. Initial symptomatic cure was achieved in 41% of vancomycin patients compared to 4% of placebo patients (1 study; 44 patients; RR 9.00; 95% CI 1.24 to 65.16). Vancomycin was significantly superior to placebo for initial bacteriologic response. Initial bacteriologic response was achieved in 45% of vancomycin patients compared to 4% of placebo patients (1 study; 44 patients; RR 10.00; 95% CI 1.40 to 71.62). No statistically significant differences in efficacy were found between vancomycin and fusidic acid, nitazoxanide, or rifaximin. No statistically significant differences in efficacy were found between metronidazole and nitazoxanide or fusidic acid. Vancomycin was significantly superior to bacitracin for initial bacteriologic response. Initial bacteriologic response was achieved in 48% of vancomycin patients compared to 25% of bacitracin patients (2 studies; 104 patients; RR 0.52; 95% CI 0.31 to 0.86). Teicoplanin, an antibiotic of limited availability and great cost, was significantly superior to vancomycin for initial bacteriologic response and cure. Initial bacteriologic response was achieved in 62% of vancomycin patients compared to 87% of teicoplanin patients (2 studies; 110 patients; RR 1.43; 95% CI 1.14 to 1.81). Bacteriologic cure was achieved in 45% of vancomycin patients compared to 82% of teicoplanin patients (2 studies; 110 patients; RR 1.82; 95% CI 1.19 to 2.78). Teicoplanin was significantly superior to metronidazole for initial bacteriologic response. Initial bacteriologic response was achieved in 71% of metronidazole patients compared to 93% of teicoplanin patients (1 study; 59 patients; RR 0.76; 95% CI 0.60 to 0.98). Only one study investigated synergistic antibiotic combination, metronidazole and rifampin, and no advantage was demonstrated for the drug combination. There was a total of 18 deaths among 1152 patients. The deaths were generally attributed to underlying disease rather than CDAD or antibiotic treatment. One study reported a partial colectomy after failed CDAD treatment.
Comment: The quality of evidence is downgraded by study quality (inadequate or unclear allocation concealment and blinding) and by imprecise results (few patients and wide confidence intervals).
The following decision support rules contain links to this evidence summary:
- Metronidazole in preference to vancomycin as the first choice in Clostridium difficile diarrhoea
Ədəbiyyat
- Nelson RL, Suda KJ, Evans CT. Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults. Cochrane Database Syst Rev 2017;(3):CD004610. .