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 last week of August 2017.
Authored By: Jamie Kisgen, Pharm.D., BCPS-AQ ID, Melissa Campo, Pharm.D., and Andre Tran, Pharm.D.
Link to post is here.
Commentary: Christmas in August? That’s how it felt this week when we heard about the FDA approval of meropenem/vaborbactam (Vabomere), for complicated urinary tract infections.
Unlike oncology, new agents for infectious diseases are rare (except for maybe hepatitis C of course). Although we are quite familiar with meropenem, the addition of vaborbactam (a non-b-lactam b-lactamase inhibitor) gives us a much-needed agent against carbapenem-resistance Enterobacteriacae (CRE) and Pseudomonas. If you are looking for a quick summary of this new antibiotic, check out the link above. Although I do not see this as a drug I will use very often, it is reassuring to have another option in the toolbox for these challenging multidrug-resistant organisms.
Please use carefully…
Article is here.
Commentary: According to the CDC, over 9,000 healthcare-associated infections are caused by carbapenem-resistant Enterobacteriaceae (CRE) each year. Severe infections involving carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains carry a high risk of mortality. Alternative antibiotics are often highly toxic (e.g., aminoglycosides and polymyxins) and/or less effective (e.g., tigecycline).
The authors of this study evaluated the clinical impact of a double carbapenem (DC) regimen in critically ill adults with documented CR-Kp. This case-control, observational two-center study included patients with a DC regimen of meropenem PLUS ertapenem (which served as a competitive inhibitor of carbapenemase) or a standard regimen such as colistin, tigecycline, or gentamicin. Of note, the observational period of this study was prior to the availability of ceftazidime/avibactam.
Forty-eight patients with DC were matched with 96 controls with a primary end point of 28-day mortality. Secondary endpoints included: clinical cure, microbiological eradication, duration of mechanical ventilation, duration of vasopressors, and 90-day mortality. The DC group may have had more severe infection, as initial occurrence of septic shock and high procalcitonin levels were significantly more frequent in this group. However, 28-day mortality was 47.9% in patients receiving standard treatment compared with a statistically significant difference of 29.2% in the DC group.
Take home: Double carbapenem therapy may be a viable option for CRE based on available evidence, but requires a larger clinical trial to confirm these observational results. More importantly, we need to see how DC regimens compare against newer antimicrobial agents like ceftazidime/avibactam or meropenem/vaborbactam before recommending them routinely.
Article link is here.
Commentary: Multidrug-resistant organisms (MDROs) are difficult to treat and lead to significant morbidity and mortality, increased lengths of stay, and excessive costs. With a limited antibiotic pipeline and the rise of antimicrobial resistance, antimicrobial stewardship programs (ASPs) have been advocated to improve appropriate antimicrobial use. To date, there is evidence demonstrating the benefits of an ASP, however, there are concerns for negative consequences if antibiotics are de-escalated or discontinued too soon based on ASP recommendations.
The authors of this study from Singapore sought to evaluate the impact on clinical outcomes when ASP interventions for inappropriate carbapenem use were accepted or rejected by primary providers. This retrospective review from July 2011 to December 2014 analyzed two groups: “accepted” interventions and “rejected” interventions. Of 220 patients, carbapenem use was inappropriate in 101 (45.9%), and a total of 158 interventions were made. There was a significant reduction in 30-day mortality in the accepted (none) versus rejected group (10 deaths, p = 0.015), but there were no differences in length of stay, hospitalization charge, or 30-day readmission rates. ASP interventions did not compromise patient safety in terms of clinical outcomes while reducing consumption.
ASPs are designed to encourage appropriate use of antibiotics and minimize resistance, but it can often be difficult to measure intervention impact on the reduction of resistance. At your institution, what is the impact of your ASP on clinical outcomes and what tools do you use to assess the effectiveness of your interventions?
Article is here.
Commentary: According to the latest hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) guidelines, risk factors for methicillin-resistant Staphylococcus aureus (MRSA) infection include prior intravenous antibiotic use within 90 days, hospitalization in a unit where greater than 20% of S. aureus isolates are methicillin resistant or the prevalence of MRSA is unknown, or patients who are at high risk for mortality.
More often than not, a patient with suspected nosocomial pneumonia will be started on vancomycin empirically. The challenge arises when deciding if it is clinically appropriate to de-escalate in the absence of a respiratory culture. Although lower respiratory tract cultures would be ideal to streamline therapy, it is not always easy to obtain such culture. One proposed intervention is the use of a rapid PCR DNA screen to determine if the patient is colonized with MRSA in the nares and discontinuing MRSA therapy if the test is negative.
This article discusses several studies that evaluated the impact of using MRSA DNA screenings in patients with pneumonia, ultimately concluding that they can provide a negative predictive value of 94% to greater than 99%. Undoubtedly, MRSA DNA screening in patients with pneumonia can be a beneficial tool that can help guide and streamline antibiotic therapy. Although the recent HAP/VAP guideline does not provide support the utilization of this screening test to direct therapy, there is new and emerging data that provides strong evidence of utilizing MRSA DNA screening to rule out MRSA as a potential pathogen in lower respiratory tract infections.
Article is here.
Commentary: The IDSA guidelines for Clostridium difficile infection (CDI) was last published in 2010, with an update in progress to be published in Fall 2017. In patients with severe CDI, the current guidelines recommend the use of vancomycin (PO) with or without metronidazole (IV) depending on if complications are present. However, in the past 7 years, our understanding of how to treat CDI has evolved significantly with emerging literature and new treatment regimens available on the market.
This retrospective cohort study from France evaluated the impact of early fecal microbiota transplantation (FMT) on survival rates in patients with severe CDI. Treatment included either medical treatment alone (n=45) or treatment with early FMT (n=66), assessing for a primary outcome of a 3 month mortality rate. Of note, FMT and antibiotic regimens varied in the study and treatment decisions were at the discretion of the clinician. Overall mortality in the study was 24.3%, of which 42.2% died in the antibiotic only group versus 12.1% in the FMT group. It was found that FMT improved survival in severe cases (0.08, 0.016-0.34, P=0.001) but not in non-severe cases (1.07, 0.02-56.3, P=.97), with a number needed to treat of 2.
This article proposes that early FMT can reduce mortality significantly and should be considered as a first-line treatment for these patients with severe CDI. Although these results are encouraging, further study is needed to determine the best timing and method for administering FMT in this setting.
As severe CDI is associated with significant morbidity and mortality, it is important for health care professionals to gain a greater understanding of this infection. It will be interesting to see what changes will be made to the updated IDSA guidelines to reflect the new literature available supporting alternative treatment approaches.
BONUS TWEET #JustForFun
Guest Contributors: 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.