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September 2008
Vol. 18, No. 9
Patient Care and Science
EIN: Difficulty Treating 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, which funds the EIN. The reader assumes all risks in using this information.

Highly resistant gram-negative infections and the lack of effective drugs to treat them are a growing problem for infectious diseases clinicians. In several recent discussions on the Emerging Infections Network (EIN) listserve, clinicians have discussed how to deal with these difficult-to-treat infections.

One thread noted the rapid evolution of resistance to quinolones in Pseudomonas aeruginosa. A member had treated a patient for urosepsis with intravenous (IV) levofloxacin and discharged him with a two-week oral course of the same drug. Before he could complete the course, the patient relapsed with a resistant strain of the bacterium.

Others reported experiences with resistant strains of Pseudomonas, as well as in E. coli and Klebsiella pneumoniae. “I avoid use of ciprofloxacin first up, as widespread use of fluoroquinolones in the community may have selected for mutations,” one member noted. “Subsequent exposure when there is high bacterial load increases the risk.”

Another member referred to a 2005 study in Clinical Infectious Diseaseson Pseudomonas resistance to quinolones. “The more you use them, the more resistance you'll see, at least on a population level,” the member said.

Another member was concerned about resistance to tigecycline developing in a patient with a Klebsiella urinary tract infection (UTI) that was already resistant to multiple drug classes. The member mentioned case reports of tigecycline treatment failures for gram-negative infections and asked for other suggestions.

Members reported both success and failure with tigecycline. One noted that only 10 percent of the drug gets into the urine, which may account for failures in treating UTIs with tigecycline. For alternatives, some suggested fosfomycin, amikacin, doxycycline, or colistin, although renal toxicity is a well-known problem for the latter.

Colistin is making an unexpected comeback due to the shortage of new antimicrobials, particularly for gram negatives. A member looking for a protocol for prescribing colistin was directed to two references: a 2007 article in Expert Review of Anti-infective Therapycomparing colistin (polymyxin E) and polymyxin B; and a pharmacokinetics case study from 2005 in Antimicrobial Agents and Chemotherapy.

In addition to the shortage of effective new drugs to treat highly resistant gram-negative infections, in some cases there is a shortage of good data on using current drugs. Case in point: a member was treating a child with cystic fibrosis (CF), allergic bronchopulmonary aspergillosis and Stenotrophomonas maltophilia resistant to at least a dozen different drugs. “If her lung function does not improve we want to admit her for IV antibiotic treatment,” the member wrote. “The question is, with what?”

Some suggestions included:

  • high-dose trimethoprim/sulfamethoxazole in combination with ticarcillin/clavulanic acid or ceftazidime
  • aztreonam in combination with amoxicillin/clavulanic acid or ticarcillin/clavulanic acid
  • tigecycline
  • inhaled tobramycin with amiloride (according to one small reportfor treating Burkholderia cepacia in CF patients, which might also work for S. maltophilia)
  • chloramphenicol as a last resort, despite the risk of aplastic anemia

For information on IDSA’s efforts to address the antimicrobial resistance crisis, see the web pages on the “Bad Bugs, No Drugs” campaign and the Strategies To Address Antimicrobial Resistance (STAAR) Act

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) and supported by funding from the Centers for Disease Control and Prevention.

EIN tracks emerging infectious diseases and keeps the public-health community up to date with issues that are currently affecting or may soon affect 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. The EIN listserve allows members to discuss new disease trends and difficult cases. Click here for more information or to join EIN.
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Cover Stories
CDC Campaigns Target MRSA, Inappropriate Antibiotic Use
2009 Clinical Practice Meeting in San Diego
IDSA Journal Club, August 2008
From the President
IDSA Ascendant
Patient Care and Science
EIN: Difficulty Treating Multidrug-resistant Gram Negative Infections
Drug Approvals, Recalls, Adverse Events Update
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ID Physicians Have Second-highest Coding Error Rate in CMS Report
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Policy and Advocacy
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IDSA Advocacy Update
Education and Resources
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Your Colleagues
In Memoriam: Thomas Weller
Members on the Move
Welcome, New IDSA Members!

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