The “New Stuff In Infectious Diseases” column pulls content from the infectious diseases community on Twitter. Commentary, relevant links and tweets are provided. This is the summary for the second week of August 2017.
Authored By: Jamie Kisgen, PharmD, BCPS-AQ ID, John D’Arcangelis, PharmD Candidate, Melissa Campo, PharmD, and Andre Tran, PharmD
[Last updated 8-15-2017]
Article link is here.
Commentary: Unlike drugs for hypertension and diabetes, inappropriate prescribing of antimicrobials not only impacts the patient, but everyone else in the community. Even with education directed towards prescribers about the risk for antibiotic resistance and a limited pipeline of new agents, inappropriate prescribing continues to happen at a staggering rate. This article raises the question of whether prescribing of antibiotics should be limited to infectious disease (ID) specialists only. As the author points out: “Providers have heard the message of antibiotic overuse and resistance over and over, but little has changed, and the stakes keep getting higher. Is it time for us physicians to hand over the antibiotic prescription pad?”
Restricting (a.k.a. protecting) all antibiotics to ID specialists sounds like a logical solution to our problem of over-prescribing and resistance. However, this may be a little extreme and unrealistic at this time. Restricting access to all antibiotics may lead to resentment from many prescribers due to the loss of autonomy. It could also impact patients by making it more difficult to obtain a prescription for antibiotics when they actually need it, because not enough ID specialists are around in the community or in the hospital to meet the demand. This could lead to people obtaining antibiotics through extreme measures such as the internet or oversees (see last week’s post). A more rational solution could be the mandatory completion of continuing medical education or certification that focuses on antimicrobial stewardship. It is very clear that something needs to be done now to reduce over-prescribing of antibiotics and development of resistance, and hopefully a happy medium to this problem can be found before extreme measures such as the one proposed in this article have to occur.
Article link is here.
Commentary: Dalbavancin, a novel second-generation lipoglycopeptide structurally related to vancomycin and teicoplanin, has unique pharmacokinetic properties and excellent in vitro activity against Gram-positive pathogens, including MRSA. It is currently FDA-approved for acute bacterial skin and skin structure infections and is being studied for additional indications, including osteomyelitis and complicated bacteremia/endocarditis. Given the long terminal half-life of the drug (346 hours!), some concerns have been raised about the potential for inducing drug resistance, especially in high inoculum, deep-seated infections.
A case report was recently published involving a patient with an MRSA central-line-associated blood stream infection, in which dalbavancin and vancomycin non-susceptibility emerged from a urine isolate collected after the patient was treated with vancomycin and dalbavancin sequentially. After susceptibility testing, the blood isolate demonstrated susceptibility to vancomycin, however, the minimum inhibitory concentrations of the urine isolate to dalbavancin, vancomycin, telavancin, and daptomycin were ≥4-folder higher than the blood-derived strain.
This first case report of VISA emergence in the setting of a dalbavancin-containing regimen should remind clinicians to be aware of the possibility of not only dalbavancin non-susceptibility, but the risk of cross-resistance to other glycopeptide agents. It will be interesting to see the results of ongoing clinical trials involving dalbavancin for deep-seated infections and whether or not lipoglycopeptides with slightly different activity (e.g., oritavancin) show similar patterns of risk of cross-resistance.
Article link is here.
Commentary: For over 60 years, we have known that tetracycline use in children under 8 years of age was linked to staining of permanent teeth. The tooth discoloration varies from yellow or gray to brown and the mechanism relates to the drugs ability to chelate calcium ions and be incorporated into teeth, cartilage and bone. Pharmacy and medical students have been told for years to avoid the entire drug class in children, fearing this adverse effect would be seen with other agents. Doxycycline, a semi-synthetic tetracycline with lower calcium binding capacity, is sometimes used in children out of necessity for the treatment of Mycoplasmal, Chlamydial, and Rickettsial infections (especially Borrelia burgdorferi the cause of Lyme Disease).
Researchers from Finland sought to determine if doxycycline exposure in children less than 8 years of age increased the risk of staining of permanent teeth similar to tetracycline. This was a single center study of 38 patients treated over a 21-year period. The average age at doxycycline exposure was 3.7 years of age (range 0.6 – 7.9 years) and average duration of therapy was 12.5 days (range 2 – 28 days). A clinical examination by a pediatric dentist (as well as a dental photograph evaluation by a 2nd blinded dentist) confirmed that none of the patients demonstrated Tetracycline-like staining or enamel hypoplasia.
Although this study had a few limitations, it does provide some comfort to providers who want to use doxycycline in children under 8 years of age. Rumor has it the American Academy of Pediatrics may be updating its warnings for Doxycycline in the next version of the RedBook…stay tuned!
Article link is here.
Commentary: According to the CDC, Clostridium difficile causes over half a million infections every year and 29,000 deaths within 30 days of the diagnosis. Using our current treatment options, anywhere between 15-25% of patients will develop a recurrence after the first episode. Recurrence rates only increase with each subsequent infection, leading many clinicians to search for new dosing strategies and alternatives.
In October 2016, bezlotoxumab (Zinplava), a human monoclonal antibody directed against C. difficile toxin B, was approved by the FDA for the prevention of C. difficile infection (CDI) recurrence. This was based on the results of two phase 3 randomized control trials, MODIFY I and MODIFY II. In these studies, use of bezlotoxumab, in addition to standard of care (vancomycin, metronidazole, or fidaxomicin), led to an absolute reduction in CDI recurrence of approximately 10%.
This new article is a post-hoc analysis of patients who were hospitalized with CDI prior to randomization, to determine if bezlotoxumab had a significant impact on 30-day readmission rates. As many of you know, this is a key quality metric for CMS and your hospital C-suite.
According to this study, patients receiving bezlotoxumab had a significant decrease in 30 day CDI-related readmission (absolute risk reduction [ARR] of 6.1%) and a numerical decrease in all-cause readmission (ARR of 3.7%). This reduction was also significant in some of the high-risk groups, including patients > 65 years of age, and patients with severe disease. However, patients who had > 1 CDI episodes in the past 6 months, were immunocompromised, or infected with the 027 strain did not have a significant reduction in 30 day readmission.
Although the results of this study are encouraging, the $3,800/vial price tag and number needed to treat of 17 make it an expensive intervention to simply decrease readmissions ($64,600 per readmission prevented). I feel a pharmacoeconomic analysis needs to be performed comparing bezlotoxumab to fidaxomicin and fecal microbiota transplant, to determine which option provides the most cost-effective approach. More head to head and combination studies could provide additional guidance as well.
Link to CDC article is here.
Commentary: Everyone loves a good papaya. However, this popular fruit may be hiding a new surprise this summer. There is currently a multistate outbreak of Salmonella kiambu and Salmonella thompson, infecting 141 people from 19 states – with 45 cases of hospitalization and one death reported from New York City.
Reports of people becoming ill from the outbreak began on May 17, 2017. Utilizing epidemiologic and laboratory evidence, it was found the Maradol papayas from the Carica de Campeche farm in Mexico may be the source of the outbreak. Both the CDC and the FDA are warning consumers to avoid eating papayas from this farm; and when in doubt, it is best to just throw it out.
The FDA is continuing their investigation, and has isolated several other types of Salmonella strains from other papayas imported from Mexico, including Salmonella agona, Salmonella kiambu, Salmonella gaminara, and Salmonella senftenberg. It is being determined if these other strains are associated with this outbreak.
Signs and symptoms of a Salmonella infection usually consists of diarrhea, fever, and abdominal pain. Typically the illness lasts 4 to 7 days, with most people recovering without the need for treatment. The FDA recommends patients should contact their health care provider if they experience diarrhea for more than 3 days, accompanied with a high fever, blood in the stool, or dehydration from vomiting.
BONUS TWEETS – MEMES!!
Guest Contributors: John D’Arcangelis, PharmD Candidate 2018, is a pharmacy student from the University of Florida College of Pharmacy and advance pharmacy practice experience student at Sarasota Memorial Hospital in Sarasota, Florida. Melissa Campo, PharmD (@melissascampo) and Andre Tran, PharmD (@InfxnSlayerJr) are PGY1 Pharmacy Practice Residents at Sarasota Memorial. They are acknowledged as contributing authors for this article.
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