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March 2012
Patient Care and Science
EIN Update: A Complex Case of Multidrug Resistant P. aeruginosa

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 a complex case of multidrug-resistant Pseudomonas aeruginosa, highlighting the need for new antimicrobials to treat serious resistant infections.

“I'm currently taking care of a 23-year-old white female who was originally admitted to an outside hospital with complaints of fever, cough, and hemoptysis,” an EIN member in Michigan wrote. A CT scan in the emergency room revealed bilateral pulmonary infiltrates, and the woman required intubation shortly after admission. She was empirically started on piperacillin/tazobactam and linezolid.

Initial bronchial cultures were all negative. The next day, the patient’s blood cultures became positive for Neisseria meningitidis, and her antimicrobials were changed to ceftriaxone. HIV testing was negative.

Several days later, the patient’s condition worsened. Another bronchoscopy was performed, with cultures growing Pseudomonas aeruginosa susceptible to colistin only. She was then transitioned to IV colistin and continued on ceftriaxone. Her mental status subsequently improved after three days, and her family noted she was awake and alert. But the patient then “became minimally responsive with increasing difficulty with oxygenation,” the member wrote. A new CT scan showed a large left upper lobe cavitary pneumonia.

“At that point she was transferred to my facility where ECMO was initiated,” the member noted, and continuous renal replacement therapy was also started. “The patient has continued to require ECMO (now day fourteen) with an inability to mechanically ventilate (Vt <20 ml).” Repeat cultures continue to grow P. aeruginosa “with copious purulent secretions and desquamative appearance to the lung tissue.”

“She has been treated at our facility with  colistin, ceftaz, and rifampin,” the member wrote, with ciprofloxacin and azithromycin also being added recently. “Any thoughts or suggestions would be appreciated.”

An EIN member in Connecticut suggested that fosfomycin might have a role. “It’s not a great stand-alone drug for P. aeruginosa, but it does have some activity and seems to be synergistic with aminoglycosides,” the member noted, citing a 2003 article from the Journal of Cystic Fibrosis, which reported on the use of fosfomycin in cystic fibrosis patients with Pseudomonas infection.

A respondent in Oregon offered a few suggestions to optimize the colistin dosage. “The target is a steady state concentration of 5 ug/ml,” the member wrote. “Serum levels are not routinely available. The best that we have, to date, are the pharmacokinetic studies of Roger Nation. Based on his study of roughly 100 patients, the suggested dosing formula to hit the 5 ug/ml target is: 5((1.5 X CrCl) +30) = the total daily dose. But you have to normalize to Body Surface Area: Total daily dose X patient’s body surface area in M2/1.73 M2. Divide total daily dose into q8h regimen.”

The member noted there is some evidence that “in the presence of the colistin, carbapenems are able to penetrate to their target despite resistance enzymes and efflux pumps,” citing a December 2011 article in Antimicrobial Agents and Chemotherapy. “I would suggest using imipenem or meropenem.”

A member in California called the case a “tragic situation. But I wonder if in the face of such a resistant profile and clinical failure, and empiric therapeutic combinations, whether in vitro studies for synergy or additive effect therapy might be justified.”

Help IDSA address rising drug resistance and the dwindling antimicrobial research and development pipeline by sharing how resistance is impacting your ability to care for patients and by alerting your representatives in Congress to the need for action. Learn more here.

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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