Medical treatment for botulism

Review question

We reviewed the evidence on the effect of medical treatment on human botulism.

Background

Botulism is a serious illness that starts suddenly and causes paralysis (an inability to use muscles). The cause of botulism is a germ called Clostridium botulinum. If the illness is left untreated, many people with botulism will die. There are four main types of botulism: adult and infant types where the intestine (gut) is infected; botulism from contaminated food; and wound botulism.

We searched for clinical trials of medical treatments for any of the four major types of botulism. We assessed the effects of treatment on the rate of deaths in hospital from any cause within four weeks of infection. We were also interested in deaths within 12 weeks, length of hospital stay, the need for a ventilator to help with breathing (mechanical ventilation), feeding by tube, and harmful events of treatment.

Study characteristics

Our searches of the medical literature revealed one relevant study, which was in infant botulism. The treatment was a single dose of a medicine made from human immune proteins (human-derived botulinum immune globulin intravenous, or BIG-IV). Fifty-nine infants received BIG-IV, and 63 infants received a placebo (inactive treatment). Each study participant was followed up for the duration of their hospitalization. This study was sponsored by the California Department of Health Services.

Key results and certainty of the evidence

There were no deaths in either group in the trial. Infants treated with BIG-IV spent, on average, about three weeks less time in hospital (i.e. 3.1 weeks versus 5.7 weeks) than infants who received the inactive treatment, and spent about three weeks less on a ventilator (1.8 weeks versus 4.4 weeks). The average duration of tube feeding in the BIG-IV group was more than six weeks less than in the placebo group (i.e. 3.6 versus 10 weeks). The risk of harmful effects of the treatment was probably no greater with BIG-IV than with the inactive treatment. The evidence was mostly of moderate certainty (low certainty for time spent on a ventilator).

The review shows that BIG-IV probably shortens hospitalization; may shorten time spent on a ventilator; and probably reduces the duration of tube feeding compared to placebo. On the other hand, we found no evidence for or against botulism antitoxin or other treatments for botulism.

The evidence is up-to-date to January 2018, when we updated the searches and found no new trials.

Authors' conclusions: 

We found low- and moderate-certainty evidence supporting the use of BIG-IV in infant intestinal botulism. A single RCT demonstrated that BIG-IV probably decreases the duration of hospitalization; may decrease the duration of mechanical ventilation; and probably decreases the duration of tube or parenteral feeding. Adverse events were probably no more frequent with immune globulin than with placebo. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.

Read the full abstract...
Background: 

Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key, but the role of other medical treatments is unclear. This is an update of a review first published in 2011.

Objectives: 

To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding, and risk of adverse events in botulism.

Search strategy: 

We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase on 23 January 2018. We reviewed bibliographies and contacted authors and experts. We searched two clinical trials registers, WHO ICTRP and clinicaltrials.gov, on 21 February 2019.

Selection criteria: 

Randomized controlled trials (RCTs) and quasi-RCTs examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food-borne botulism, wound botulism, and adult intestinal toxemia). Potential medical treatments included equine serum trivalent botulism antitoxin, human-derived botulinum immune globulin intravenous (BIG-IV), plasma exchange, 3,4-diaminopyridine, and guanidine.

Data collection and analysis: 

We followed standard Cochrane methodology.

Our primary outcome was in-hospital death from any cause occurring within four weeks from randomization or the beginning of treatment. Secondary outcomes were death from any cause occurring within 12 weeks, duration of hospitalization, duration of mechanical ventilation, duration of tube or parenteral feeding, and proportion of participants with adverse events or complications of treatment.

Main results: 

A single RCT met the inclusion criteria. Our 2018 search update identified no additional trials. The included trial evaluated BIG-IV for the treatment of infant botulism and included 59 treatment participants and 63 control participants. The control group received a control immune globulin that did not have an effect on botulinum toxin. Participants were followed during the length of their hospitalization to measure the outcomes of interest. There was some violation of intention-to-treat principles, and possibly some between-treatment group imbalances among participants admitted to the intensive care unit and mechanically ventilated, but otherwise the risk of bias was low. There were no deaths in either group, making any treatment effect on mortality inestimable. There was a benefit in the treatment group on mean duration of hospitalization (BIG-IV: 2.60 weeks, 95% confidence interval (CI) 1.95 to 3.25; control: 5.70 weeks, 95% CI 4.40 to 7.00; mean difference (MD) -3.10 weeks, 95% CI -4.52 to -1.68; moderate-certainty evidence); mechanical ventilation (BIG-IV: 1.80 weeks, 95% CI 1.20 to 2.40; control: 4.40 weeks, 95% CI 3.00 to 5.80; MD -2.60 weeks, 95% CI -4.06 to -1.14; low-certainty evidence); and tube or parenteral feeding (BIG-IV: 3.60 weeks, 95% CI 1.70 to 5.50; control: 10.00 weeks, 95% CI 6.85 to 13.15; MD -6.40 weeks, 95% CI -10.00 to -2.80; moderate-certainty evidence), but not on proportion of participants with adverse events or complications (BIG-IV: 63.08%; control: 68.75%; risk ratio 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to -0.11; moderate-certainty evidence).

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