Two recent developments limiting antibiotic use could have a secondary benefit of reducing Clostridium difficile infections, which have been the bane of infection preventionists since emerging in a highly virulent strain some 15 years ago.
The first is the FDA’s recent safety warning1 that clinicians should only use fluoroquinolones on the following three conditions if no other antibiotic alternative exists:
- acute bacterial sinusitis,
- acute bacterial exacerbation of chronic bronchitis, and
- uncomplicated UTIs.
The FDA cited serious, “potentially permanent” side effects of the muscles, joints and nervous system associated with the following fluoroquinolones:
- ciprofloxacin and cipro extended release,
- levofloxacin, and
- generic ofloxacin.
“These medicines are associated with disabling and potentially permanent side effects of the tendons, muscles, joints, nerves, and central nervous system that can occur together in the same patient,” the FDA stated in the drug communication.
In addition, the FDA revised its strongest warning — the “boxed warning” — and updated other parts of the labels for the aforementioned drugs.
“For some serious bacterial infections the benefits of fluoroquinolones outweigh the risks, and it is appropriate for them to remain available as a therapeutic option,” the FDA stated.
Though not mentioned by the FDA, the action could reduce Clostridium difficile infections, which can establish in the gut after administration of fluoroquinolones and other antibiotics. Some studies2 have found fluoroquinolones may increase onset of C. diff, so reductions in administration of this drug class could have a side benefit of reducing gut onset of the enteric pathogen.
Cut Back Duration
In another development that could favorably affect C. diff rates, the Infectious Diseases Society of America (IDSA) is advising limited duration of antibiotic courses to treat hospital-associated pneumonia (HAP) and ventilator-associated pneumonia (VAP). These infections affect hundreds of thousands of patients a year and generate high volumes of antibiotic use. In conducting a review of the literature and considering other factors, IDSA is recommending that antibiotic treatment should not go beyond a week. Of course there will be individual circumstances and exceptions, but in general, antimicrobials administered beyond seven days for these patients have little additional therapeutic benefit and can select out resistant bacteria and trigger C. diff infections by wiping out commensual bacteria in the gut.
Hospital Infection Control & Prevention talked to lead author Andre C. Kalil, MD, an infectious disease physician at the University of Nebraska Medical Center in Omaha, about the guidelines.
“Pneumonias are the top cause of use of antibiotics in ICUs in the United States,” he says. “It is logical to think it must be one of the top causes of C. diff just because of this high frequency of use. C. diff is definitely something that we are very concerned about. This is not a preventive guideline, but we believe that more judicious use of antibiotics could curtail C. diff as well.”
The IDSA and the American Thoracic Society guidelines call for antibiotic administration for “seven or fewer days” for HAP and VAP.
“We did an extensive review of the literature to make sure that this is the most effective [time period],” Kalil says. “Sure, there will be exceptions as we note in the guidelines, but this should be highly effective [to treat infections], and on top of that we gain several other benefits of having shorter courses: less side effects, less C. diff, less drug resistance, and lower costs.”
A key aspect of the guidelines calls for all hospital clinicians to create antibiograms to clearly show the range of susceptibility and resistance in the particular pathogens causing infections in their hospital. This knowledge will inform therapy and allow allow maximum benefit in the shortest duration, the guidelines state.
“We believe this is really important for the accuracy of treatment of VAP and HAP because you really have to know your hospital flora, your ICU flora — what normally infects the patients in your hospital?” Kalil says. “Then you are able to have much more individualized and precise care with your antibiotics. This type of approach will not only benefit the patient by delivering the right drug but also avoid the mistakes of giving unneeded drugs and exposing the bugs [enough] to develop resistance. We think this is something that will benefit both individual patients and society.”
Though antibiotic stewardship goes beyond the scope of the guidelines, it goes without saying that creating antibiograms could inform judicious use of drugs as a part of such programs.
The new guideline updates the 2005 IDSA recommendations, which recommended different treatment durations for the various bacteria that cause HAP and VAP.
- FDA Drug Safety Communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects. July 26, 2016: http://bit.ly/2aN14S3.
- Brown KA, Khanaferb N, Danemanc N, et al. Meta-Analysis of Antibiotics and the Risk of Community-Associated Clostridium difficile Infection. Antimicrob Agents Chemother 2013;57:2326-2332.
- Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016;63:1 -51.