Posted on behalf of Marian Turner
As enterohaemorrhagic Escherichia coli continues to cause an unprecedented number of life-threatening infections in Europe, American medics are questioning Germany’s approach to the outbreak, according to the New York Times.
It reports that “the accepted medical wisdom in the United States is that E. coli infections should not be treated with antibiotics at all”. And it quotes Phillip Tarr, paediatrician at Washington University, saying that treating patients with antibiotics to which the infecting bacteria are resistant is especially dangerous, as this provides the infecting strain with a competitive advantage. The NYT article also says that antibiotics can increase the chances of kidney failure, although it does not explain how. (The reason is that antibiotics prompt the bacteria to produce more Shiga toxin, the chemical responsible for the damage to blood vessels in the kidneys that leads to renal failure during severe EHEC infections.)
Although you wouldn’t realize it from the NYT article, German doctors and microbiologists are well aware of these important – but not novel – considerations. The German health authorities have told the press and the public from the outset that the bacteria show unusual antibiotic resistance characteristics, but they have continually stressed that they were not using antibiotics to treat these infections.
The antibiotic resistance genes provide useful information to epidemiologists and microbiologists who are trying to trace the source of the outbreak and understand the virulence of the bacteria.
The standard treatment for the severe diarrhea and kidney failure that can result from EHEC infections is fluid replacement and dialysis. But these traditional methods are simply not enough to save the lives of many severely ill patients in this outbreak. Ten days ago, German clinicians turned to a new monoclonal antibody therapy called eculizumab. Jan Kielstein, nephrologist at the Hannover Medical Clinic, says that 200 patients have now been treated with eculizumab, with promising outcomes, although it is too early to definitively align these recoveries with the drug.
In the past two days, however, some German hospitals have begun using antibiotic treatments. “After intense discussions there has been a decision to recommend antibiotics in some cases under tight regulation of patient responses,” says Angelika Fruth from the Robert Koch Institute, the federal agency responsible for disease control.
The German Association of Infection Biology (DGI) released a statement on the use of antibiotics this morning. It states that the use of certain antibiotics associated with enhanced toxin secretion (including fluoroquinolones and aminoglycosides) are still not recommended for EHEC infections. But it advises that the antibiotic carbapenem may be used in patients showing neurological complications and secondary infections. Kielstein says “in vitro tests show that this antibiotic is effective against this E. coli strain, and that the bacteria do not produce more Shiga toxin in response to it”.
The DGI statement also states that targeted reduction of intestinal bacteria with the antibiotic rifaximin is recommended in exceptional cases of EHEC persistence.
The NYT article also quoted Timothy Jones, the state epidemiologist in Tennessee, who said: “Having a strain that is virulent is not unusual”. There are indeed multiple strains of E. coli that cause infection in humans. But the number of cases of the life-threatening complication hemolytic uremic syndrome (HUS) that have arisen from this outbreak (so far more than 470 cases out of around 1500 infections) is a dramatically higher proportion than usual. In a typical year there are approximately 1000 EHEC infections in Germany, and around 65 of these cases progress to HUS. This suggests that these bacteria, of the O104 serotype but believed to be a completely new strain, are indeed much more virulent than previous strains.