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EIN Update: MDR Gram-Negative Osteomyelitis 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.

EIN members recently discussed multidrug-resistant (MDR) osteomyelitis infections caused by Gram-negative bacteria, highlighting the difficulty of these cases.

“I have a patient with limb-threatening infection with osteomyelitis from [an] open fracture, now with fixation hardware who has MDR Stenotrophomonas,” an EIN member in Florida wrote. The patient’s bacterial isolate was “resistant to all antibiotics,” including sulfamethoxazole/trimethoprim, piperacillin/tazobactam, rifampin, and tigecycline: “Intermediate to levofloxacin, moxifloxacin MIC of 2, [and] chloramphenicol less than 2.

“He is now on [doxycycline] and levofloxacin,” the member added, with his last culture “still with light growth. Would the way to go be the use of combination chloramphenicol, with moxifloxacin or monotherapy with chloramphenicol?”

A respondent in California suggested a high dose quinolone. Another respondent in Florida shared several points regarding Stenotrophomonas infections:

  • The best activity for fluoroquinolones: moxifloxacin > levofloxacin > ciprofloxacin.
  • Biofilm production is common, and fluoroquinolones and minocycline penetrate well. (Trimethoprim/sulfamethoxazole and β-lactams do not.)
  • Minocycline has very good in vitro susceptibility to Stenotrophomonas.
  • In vitro susceptibility testing poorly correlates with in vivo effectiveness with Stenotrophomonas.
  • Multiple stains of Stenotrophomonas with different susceptibility levels exist in high inoculum infections.
  • Combination antibiotics may be effective even when one or more of the antibiotics was tested to be resistant.

The EIN member provided several references:

A New York State EIN member suggested using a high-dose quinolone first, but noted that “if appropriate lab testing suggests ‘sensitivity’ of aztreonam + clavulanic acid (use amox-clav to test), an infusion of ticar-clav (continuous) along with intermittent doses of aztreonam can be considered. Sometimes the clavulanic acid will inhibit the betalactamase to allow aztreonam to be active.”

In a second case, an EIN member in Georgia reported “a patient with a culture confirmed pelvic osteomyelitis with cultures taken from the operating room growing a Pseudomonas aeruginosa,” resistant to cefepime, piperacillin/tazobactam, imipenem, ciprofloxacin, ticarcillin/clavulanate potassium, aztreonam, and colistin, that was only susceptible to aminoglycosides.

“He has progressive renal failure, now with creatinine >5,” the member continued. “We are wondering if anyone has advice on how best to treat this infection? Any data on combination therapy, even with drugs to which he is resistant?”

“The short answer is colistin plus meropenem—even though the isolate is resistant to both,” a respondent in Oregon wrote. “Another thought is to apply to FDA for investigative use of parenteral fosfomycin.”

An EIN respondent in Utah noted “some limited data that synergy between meropenem and ciprofloxacin or meropenem/colistin may be obtained even with resistant strains,” citing a 2008 article in Antimicrobial Agents and Chemotherapy. “These authors did time-kill studies as opposed to checkerboard testing as they feel it is more sensitive and accurate to predict synergy.”


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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