麻豆传媒

PHILADELPHIA -- Fecal microbiota transplant (FMT) cleared a carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) infection in a teenage girl, researchers said here.

The 13-year-old girl now appears free of the resistant organism, said from Jefferson University Hospitals in Philadelphia, and Stephen Eppes, MD, of Christiana Care Health System in Newark, Del., pointing out that her group used the FMT technique that is becoming the standard of care for Clostridium difficile infection.

"This case reports the first use of fecal microbiota transplant to eradicate colonization with K. pneumonia," Freedman said. "The favorable outcome suggests that fecal transplant is an effective method for decolonization of carbapenem-resistant Enterobacteriaceae from the gastrointestinal tract. It may also be useful for other multidrug resistant pathogens such as vancomycin-resistant enterococcus."

In a presentation at the annual IDWeek conference, the authors described the case of the patient who presented in October 2010 with persistent otitis media and otomastoiditis. Her operative cultures grew Pseudomonas aeruginosa, and she was treated for several weeks with broad spectrum antibiotics, specifically piperacillin/tazobactam and levofloxacin. During her therapy she continued to have pain and positive superficial cultures.

She was readmitted in November 2010 with persistent fever. She was finally diagnosed with hemophagocytic lymphohistiocytosis. Antibiotics were discontinued and she was treated with high-dose corticosteroids and etoposide, with initial clinical improvement. In January 2011 she developed a fever.

Her blood culture grew K. pneumoniae which was carbapenemase-positive by the modified Hodge test. The test showed resistance to amoxicillin/clavulanic acid, ampicillin, ampicillin/sulbactam, cefazolin, cefotaxime, ceftriaxone, meropenem, and piperacillin/tazobactam, imipenem, tigecycline. She had intermediate resistance to gentamicin and doripenem.

Despite administration of antibiotics with in vitro activity, her blood cultures remained persistently positive for the next 33 days. During that time she also developed septic arthritis of one shoulder and both hips.

Searching for answers, "I cast myself upon the waters of the Internet -- and, lo, a wondrous group of consultants came forth to help," Freedman explained. Based on their advice, Freedman began an antibiotic treatment regimen that included combination therapy of extended infusion doripenem, colistin, rifampin, and plazomicin, an investigational aminoglycoside now in phase III trials. After 6 weeks, that treatment eradicated the bloodstream infection. Septic joints were washed out with Polymyxin B.

But while active infection was gone, Freedman said she worried that colonization of the drug-resistant K. pneumonia would increase the risk for recurrence, especially because the patient was immunocompromised from her treatment. Testing showed she still had K. pneumoniae in her stool although she was asymptomatic for months.

In October 2012, 7 months after antibiotics were stopped, she developed severe osteomyelitis of the right femur and cultures grew the same K. pneumoniae. For more than a year, stool cultures grew the carbapenemase-positive bacteria and little else. That prompted Freedman and the treatment team to perform FMT, 18 months after the initial infection.

The investigators searched in the family for a donor and found that the girl's half-brother was fully immunized, had not received antibiotics recently, and had stools that were negative for C. difficile, other resistant bacteria, ova and parasites, and pathogenic viruses.

The patient and the team opted for a nasoduodenal tube implant, rather than enema or colposcopy. She underwent 48 hour bowel cleansing with polyethylene glycol and received omeprazole prior to transplant.

Immediately prior to the procedure, 25 to 30 g of donor stool were homogenized with 60 ml normal saline for 2 minutes. The suspension was filtered twice through unbleached coffee filters. Then 25 ml of filtrate was administered and the patient remained semi-upright for 1 hour, the authors explained.

She experienced mild, transient nausea, but the procedure was well tolerated, they added.

The K. pneumoniae was not detectable in a stool sample 2 weeks after FMT, they reported. Additionally, it was not detectable in four stools over the next 8 months. There was no further clinical evidence of bacterial infection. No complications from transplant were experienced.

"The patient's hemophagocytic lymphohistiocytosis is now in remission," Freedman said. "The bad news: severe deconditioning and aseptic necrosis of both hips which will require bilateral hip replacements."

Freedman told 麻豆传媒 that she believes that the girl will be able to receive standard antibiotic prophylaxis when the hip surgery is performed. "She still has a lot of mobility problems and some psychological problems associated with being in isolation units for months," she said.

Freedman said the patient was on a ward with bone marrow transplant patients and she worried constantly that the K. pneumonia would infect others, but that did not occur.

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