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October 2010
Patient Care and Science
EIN Update: Multidrug-Resistant Gram-Negative Infections

The Emerging Infections Network (EIN) is a forum for infectious diseases consultants and public health officials to report information on clinical phenomena and epidemiological issues with public health significance. Any diagnostic or therapeutic recommendations and all opinions presented are those of the individual contributor. They do not necessarily represent the views of EIN, IDSA (EIN’s sponsor), or the Centers for Disease Control and Prevention (CDC), which funds EIN. The reader assumes all risks in using this information.

A recent EIN discussion highlighted the difficulty of treating multidrug-resistant (MDR) gram-negative bacterial infections and the lack of effective antibiotic options.

“I am seeing an 18-year-old male with right-sided obstructed uropathy due to stones,” an EIN member in California wrote. Over two months, “he has developed a highly resistant Pseudomonas aeruginosa in urine culture. The urologist will not want to do anything with him until [the] urine can be sterilized, and his urine culture isolate is impossible to treat, resistant to amikacin, tobramycin and gentamicin, quinolones, cefepime, imipenem, piperacillin and tazobactam, aztreonam, ceftazidime, etc.”

After being hospitalized with a high fever, low blood pressure, shaking chills, and rigors, the patient was given ciprofloxacin intravenously “even though the MIC was 4 (resistant). The MIC for cipro was the lowest; all other antibiotics were > 16, 32, and 64. I am worried,” the member wrote. “What would you do?”

A respondent in California suggested a “continuous infusion of meropenem, perhaps 6 grams/day,” while a Texas respondent offered methenamine and colistin as treatment options. Colistin “ought to cover most Pseudomonas, though the last one I tested was resistant to colistin as well as everything else.”

An EIN member in Pennsylvania advised checking “what the MIC is for colistin. If it’s less than 4 mcg/mL, then use that drug as your primary agent. If the MICs for all carbapenems and aminoglycosides are too high to consider using a high dose of one to help treat a urine infection, then consider using high-dose fosfomycin (e.g., 2 - 6 grams q 6 hours) in combination with colistin, or some other agent.” The member cited a related article in the February 2010 issue of Clinical Microbiology and Infection.

Other members’ suggestions included polymyxin B/colistin testing and checking susceptibilities to colistin and doripenem. “You probably have one last chance at a definitive procedure before there are no other options,” a respondent in Connecticut warned.

“While colistin might be useful in the treatment of what now appears to be urosepsis, it is unlikely to help sterilize the urine,” an EIN member from Maryland wrote. “Colistin and polymyxin B are excreted by non-renal routes,” the member added, citing a November 2008 article in Clinical Infectious Diseases.

Another Pennsylvania respondent advised “a short course of rifampin (600 mg q 12 hours)” with one of three drugs: meropenem, cipro, or colistin. “This multi-drug combination should prevent P. aeruginosa bacteremia.” The member highlighted two articles related to rifampin: A March 1992 article and an October 1984 article, both from Antimicrobial Agents and Chemotherapy.

A Georgia member described a similar difficult case: A female patient “who has common variable immunodeficiency syndrome and Pseudomonas pneumonia that has gotten progressively more resistant on antibiotics. It currently is resistant to everything tested, including doripenem, [and the] MIC for colistin is 3.”

An Ohio EIN member, meanwhile, described the case of a 19-year-old female patient with cystic fibrosis, who was diagnosed as an infant and has been on a multitude of antimicrobial agents. The woman was infected with a multidrug-resistant Acinetobacter ursingii isolated from sputum.

“The organism is resistant to all aminoglycosides, all carbapenems, quinolones, and beta-lactam agents (except piperacillin—she has had anaphylaxis to this antibiotic and has multiple other antibiotic allergies),” the member wrote. “The MIC for colistin is 8 ug/mL (resistant). [It is also] resistant to tigecycline. Any thoughts on treatment?”

A Georgia member suggested obtaining synergy panels, while a California respondent advised considering “inpatient penicillin desensitization.”

Another EIN member in California asked if the patient was infected or perhaps just colonized. “If so, aerosolized colistin should probably be the backbone agent,” the member wrote. “The local PK/PD of aerosolized colistin in airways may be sufficient to cover an 8 mcg/ml organism. Consider addition of rifampin for synergy based on impressive animal data and published retrospective clinical studies.”

Other resources related to MDR gram‐negative organisms and treatment include a recent paper reviewing the current epidemiology of these infections in the United States, published in a November 2010 supplement of Infection Control and Hospital Epidemiology, and an article in the August 2010 issue of Current Opinion in Infectious Diseases. EIN is also planning a member survey to examine clinicians’ experiences with MDR Enterobacteriaceae infections and other gram-negative bacteria.


E-mail the Emerging Infections Network.

The Emerging Infections Network (EIN) is a provider-based sentinel network designed to help the public health community detect trends in emerging infectious diseases.

A joint project of IDSA and the Pediatric Infectious Diseases Society (PIDS) with funding from the Centers for Disease Control and Prevention (CDC), EIN tracks emerging infectious diseases and keeps the public health community up to date with new disease trends, difficult cases, and other issues affecting members’ clinical practices. The Network provides a great opportunity for members to share knowledge quickly across large geographical distances. Both IDSA and PIDS members are eligible to join. Click here for more information or to join EIN.
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