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European E. coli Outbreak Sheds New Light on Treatment Strategies

It is an accepted fact among medical experts that an E. coli infection should not be treated with antibiotics, as these drugs may worsen illness. But a new review of strategies used to treat victims of last year’s European E. coli outbreak shows that a combination of two or more antibiotics may have helped patients recover from hemolytic uremic syndrome (HUS) – a potentially fatal complication of E. coli infection.

The 2011 outbreak, centered in Northern Germany, was characterized by an unusually high number of HUS cases. Out of more than 4,000 people sickened by the E. coli O104:H4 bacteria, 22 percent developed this life-threatening condition. By contrast, E. coli O157:H7, the most common Shiga toxin-producing E. coli (STEC) in the United States progresses into HUS in 5 to 10 percent of patients.

HUS occurs when the Shiga toxins released by E. coli bacteria damage blood vessels, preventing adequate blood flow as red blood cells get clogged in the vessels. Deprived of blood, the kidney cannot perform its function of expelling toxins through urine.

Antibiotics are thought to increase a patient’s chance of developing HUS by increasing bacterial death and triggering the release of more Shiga toxins. But a study published this week in BMJ suggests that some antibiotics may actually help treat the kidney disease.

Scientists reviewed 298 cases of HUS treated at 23 hospitals in Northern Germany during the 2011 outbreak, finding that patients treated with at least two antibiotics were less likely to experience seizures, did not require intestinal surgery and exhibited no signs of toxic shock. The death rate among these individuals was lower than among other patients.

“As antibiotics seem to improve, but definitely do not worsen, the course of the infection we believe that they are beneficial in the later stages of the disease when the prodromal phase with diarrhoea has nearly subsided,” conclude the authors – a team of 62 medical and microbiological experts.

The two antibiotics used most commonly were meropenem and ciprofloxacin. Rifaximin was given to patients in the intensive care unit. All of these drugs were administered at only one hospital included in the study. Other treatment centers did not use antibiotics.

Researchers also found that stool samples from these patients tested negative for the bacteria an average of 8 days before those of other patients.

These findings are similar to those of a previous study which found that the antibiotic azithromycin also shortened the time that individuals shed E. coli O104:H4 after infection.

Research on the effect of antibiotics on individuals with E. coli O157:H7 infections, on the other hand, has overwhelmingly suggested that these drugs are harmful, not beneficial, to HUS patients. A study from the Washington University Medical Center in St. Louis published in March found that children who were administered antibiotics while infected with E. coli O157:H7 were more likely to develop HUS.

This week’s BMJ study also questioned the effectiveness of certain treatment strategies that have shown promise in the past. One of these is use of the drug eculizumab, which functions by blocking proteins that inhibit kidney function. Eculizumab has been approved for use as a treatment for atypical HUS in the U.S. and in Europe. A previous study of the European E. coli outbreak showed that this medication led to recovery in three 3-year-old children suffering from HUS, all of whom had not responded to other treatments.

However, the BMJ study, which examined adult cases, found that eculizumab did not halt the progress of HUS among these patients.

In fact, “The severity of haemolytic uraemic syndrome was worse than in the rest of the study population,” note the authors.

Another strategy that did not prove effective according to this study was plasmapheresis, a therapy that removes blood plasma, treats it and returns it to the patient’s body. The German Society of Nephrology recommended this treatment at the beginning of the 2011 E. coli O104:H4 outbreak because it is thought that the process might remove Shiga toxin from the bloodstream.

Out of the 298 patients included in the study, 251 (84 percent) were treated with plasmapheresis. But researchers found that the patients who did not receive this therapy recovered at the same rate as those who did.

The authors suggest that studies concluding that plasmapheresis is an effective treatment may have overlooked the fact that it was administered at the peak of disease activity, after which the disease would have declined anyway.

“These results question the current recommendation to use plasmapheresis as a standard treatment in adults with enterohaemorrhagic E coli associated haemolytic uraemic syndrome and are in agreement with the experience of paediatric nephrologists, who encounter shiga toxin induced haemolytic uraemic syndrome more often than doctors treating adults and use plasmapheresis only rarely.”

The full study is available on BMJ’s website.

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