Richard L. Oehler, MD
Professor, USF Division of Infections Diseases
Editor, IDPodcasts platforms
Since 2004, I have tried to make IDWeek (formerly known as the “IDSA annual session”) a regular annual event on my professional meeting calendar. Usually held in October, I find this scientific meeting to be a terrific way to connect with long lost colleagues and former fellows, update myself on new science in the form of freshly published abstracts and recently published research, and to refresh my core knowledge in infectious diseases by attending state-of-the-art symposiums and other conference sessions.
This year, IDWeek 18 was held in San Francisco, California from October 2 through October 7. Though the Moscone Center is currently undergoing renovations, making getting around the convention center and Yerba Buena area somewhat more difficult, the pleasant fall San Francisco weather made up for some of the city’s inconveniences.
Conference days at IDWeek can be busy–it is possible to attend as many as 11 hours of scientific sessions each day, and even more if you participate in some of the affiliated (i.e., industry sponsored satellite) meetings. As much as I tried to attend as many sessions as I possibly could, I found my few days at IDWeek to be a balance of scientific meetings, poster sessions, industry exhibits, and connecting (and reconnecting) with friends and colleagues.
As far as the scientific sessions I attended, I needed a few days to reflect on what I had learned before I could put it together in my mind. Now, after being back for a couple of weeks, my chief takeaways from IDWeek are as follows:
Non-tuberculous mycobacterial (NTM) Infections
There was an excellent session on nontuberculous mycobacterial (NTM) infections featuring information on both Mycobacterium avium complex (MAC) and rapid grower mycobacterial (RGM) infections (chiefly Mycobacterium abscessus complex). The presenters made clear the importance of achieving the clinical and microbiologic diagnosis of nontuberculous mycobacterial disease. Traditional diagnostic criteria, of course, emphasize the importance of clinical symptoms, radiographic changes and the exclusion of other diagnoses. The session emphasized the value of a microbiologic diagnosis afforded by either two positive sputum specimens, one BAL specimen and/or appropriate histopathology. The presenters mentioned the need to consider surgical resection of NTM lesions in the presence of geographically discrete disease or when there is failure to respond to medical therapy. Aminoglycoside therapy with amikacin continues to be a critical component of induction therapy in patients who are initiated on an antimycobacterial regimen, but toxicity concerns with aminoglycosides should always be kept in mind. Patients with extensive structural lung disease, resistance to macrolides, and/or persistent smear positivity all are likely to experience poor response to treatment. Similarly, in Mycobacterium abscessus complex disease, the importance of the erm (41) gene as a factor in the treatability of lung disease was emphasized. A significant predictor of progression is low BMI and either bilateral and/or cavitary disease. Some promising new therapies for refractory disease include clofazimine, bedaquiline, and the oxazolidinones; inhaled amikacin and inhaled nitrous oxide therapy may show some promise. Nontheless, NTM lung disease continues to be a frustrating disorder to treat in many severely affected patients.
HIV Disease and Pre-exposure Prophylaxis (PREP)
I was fascinated by a discussion regarding implantable devices useful in preexposure prophylaxis (PREP) for HIV infection. Such devices would be analogous to the Nexplanon contraceptive implant, which provides as much as 3 years of continuous pregnancy prevention. The implants would need to contain extremely potent long-lasting antiretrovirals given their compact size and anticipated life expectancy.
In other HIV news, the recent New England Journal study utilizing Ibalizumab (N Engl J Med 2018; 379:645-654.) in persons with multidrug-resistant HIV was discussed. In this phase 3 trial, 40 heavily treatment experienced patients with multi class antiretroviral resistance were included in the study. After a seven-day control period, a 2 g loading dose was given and functional monotherapy was observed for 7 days. The patients were then started on a regimen optimized to include ≥ 1 fully active agent. Eighty-three percent (83%) of the patients who completed the study achieved the primary endpoint ≥ 0.5 log drop in their viral load after the loading dose (statistically significant). About 43% at week 24-5 had undetectable viral loads. Other advanced therapies discussed during this HIV symposium included a phase 3 trial utilizing fostemsavir, a GP120 blocking agent that inhibits HIV attachment to CD4, PRO 140, a monoclonal antibody against CCR5, and Doravirine, a next generation NNRTI for treating HIV-1 infection. Doravirine has demonstrated non-inferiority to Ritonavir-boosted Darunavir and non-inferior efficacy to Atripla (week 48) in twin phase 3 clinical trials.
Staphylococcus aureus infections
In a symposium on the optimal management of Staphylococcus aureus infections, the authors attempted to answer several pressing questions regarding disease management. Regarding the optimal agent for invasive MSSA infections, the authors presented evidence suggesting that cefazolin therapy is probably better than nafcillin (McDaniel. CID 2017 Jul 1;65(1):100-106.) , but that some caution should be exercised with infective endocarditis and other deep-seated infections. In addition, some MSSA strains exhibited what was called the Cefazolin inoculum effect (CzIE), which resulted in the development of high MICs (≥ 16 ug/ml when the strains were incubated with high colony concentrations of MSSA (~107 CFU/mL) versus standard colony counts (~105 CFU/mL). The authors concluded that the clinical significance of CzIE is unclear. For treatment of MRSA bacteremia, the speakers presented data suggesting that for MRSA bacteremia with a vancomycin MIC ≥ 1.5, an early switch to daptomycin was associated with better outcomes. Furthermore, in a multicenter retrospective cohort in cases of MRSA bacteremia with a vancomycin MIC > 1, failure rates were similar and there was less kidney injury in the daptomycin group. Regarding whether combination therapy is useful in the treatment of Staphylococcus aureus bacteremia, data was presented (Thwaites, et. al. Lancet 2018;391:668-78.) suggesting that there was no 30 or 90 day mortality benefit in the addition of a beta lactam plus a second agent (typically, rifampicin, a fluoroquinolone, an aminoglycoside or fosfomycin) except for adding rifampin when there is prosthetic material. When considering oral stepdown therapy for the treatment of endocarditis, there have long been questions about how effective partial or fully oral regimens are for the treatment of Staphylococcus aureus endocardits. This is particularly true in cases where a prolonged course of IV therapy is not possible or carries significant safety risks. The recent NEJM POET study (Iverson. NEJM 2018) looked at 400 patients with left-sided gram-positive endocarditis and compared outcomes in those who received at least 10 days IV therapy and then were either switched to oral therapy or continued on intravenous agents. The most common oral regimens were either dicloxacillin plus rifampin or amoxicillin plus rifampin. The findings applied to MSSA only and in patients with no extracardiac complications. The study showed that in patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continuing intravenous antibiotic treatment. However, the same results do not apply to MRSA cases. Lastly, regarding salvage options for highly resistant Staphylococcus aureus, data was presented suggesting some utility for the combination of daptomycin and ceftaroline based upon a recent multicenter observational study (Zasowski, et. al. AAC 2017).
Opioid Use Disorder
Many clinicians attended a session on the importance that infectious diseases providers can play in the management of opioid use disorder when we intervene for infectious complications of their substance use. This discussion included information on so-called “supervised safer injection facilities” (SIS) where substance users can safely inject IV drugs under the nonjudgmental supervision of healthcare providers. Nearly 100 of these SIS facilities are in existence in Canada, Europe and Australia, but so far, are only apparently being considered or debated in the United States. The symposium presenters asserted that literature suggests that such supervised facilities reduce infectious diseases transmission, improve overdose morbidity and mortality, increase access to healthcare, do not increase crime or public disorder, and are cost effective. It remains to be seen if such facilities gain a foothold in U.S. communities (such as San Francisco) with significant IVDA populations.
Klebsiella pneumoniae, CRE, and HvKP
In a symposium regarding the “Big Beasts” of infectious diseases, two “Big Beasts” of Klebsiella pneumoniae were discussed, including hyper virulent Klebsiella pneumoniae (HvKP) and, Carbapenemase-producing Klebsiella pneumoniae (CRKP). First described in Taiwan in the 1980s as a cause of pyogenic liver abscess, HvKP is an emerging cause of community-acquired infections in immunocompetent hosts. This strain of Klebsiella can produce a variety of systemic manifestations, including necrotizing fasciitis, osteomyelitis, and meningitis. Fortunately, HvKP appears to be less likely to demonstrate multidrug resistance in comparison to “classic” Klebsiella pneumoniae. CRKP continues to become a more significant cause of hospital-acquired infections, most recently associated with duodenoscopes. Emerging treatments for carbapenemase resistant Enterobacteriaceae (CRE) include cefazidime-avibactam, plazomycin (a new novel aminoglycoside), meropenem-vaborbactam, imipenem-relabactam, aztreonam-avibactam, and cefiderocol. There is concern that these twin strains may share resistance factors via plasmid-related convergence, leading to hyper virulent MDR Klebsiella pneumoniae.
The management of febrile neutropenia was discussed in a separate symposium with regard to bloodstream infections, particularly those with ESBL positive Enterobacteraceae. The recent MERINO trial (Harris, et. al. JAMA. 2018;320(10):984-94.) involved 26 hospitals worldwide and looked at 30 day mortality when Escherichia coli and Klebsiella pneumoniae ESBL positive bloodstream infections were treated with piperacillin-tazobactam versus meropenem. This study found that the 30-day mortality was significantly higher (12.3%) in the Piperacillin-Tazobactam group than in the meropenem (3.7%) group. Conversely, the mortality associated with carbapenemase-resistant gram-negative bacteremia was significantly greater, suggesting that carbapenem use should still be restricted to reduce the emergence of carbapenemase-resistant Pseudomonas, Acinetobacter and Enterobacteraceae. A study by the European conference on infections including leukemia published by Mikulska in the Journal of infection (Mikulska, et. al. J Infect 2018;76(1):20-37.) was also discussed. This review showed no reduction in mortality through the common use of fluoroquinolone prophylaxis in prolonged neutropenic patients (> 7 days), although rates of bloodstream infection and fever episodes were decreased. The review suggested that fluoroquinolone prophylaxis should be utilized in high-risk patients only and be dependent upon local epidemiology and practice.
Fun and Games
Unfortunately, IDWeek is far too large a meeting for the totality of its expansive and compelling scientific program to be described here. For me, a highlight was clearly the 3rd annual ID Bug Bowl. This is the annual infectious diseases quiz competition that caps off the meeting, usually on the evening prior to the closing plenary. Even though we here at IDPodcasts still lay first claim to the term “Bug Bowl,” (Our “Bug Bowl: Bacteriology edition” podcast appeared online in 2015 the year before the first IDWeek session was inaugurated in 2016), we still try to attend every year to take in some of the excitement and “infectious” enthusiasm (pun intended) conveyed by the medical students, residents, and infectious diseases fellows from 3 or 4 different institutions who are its participants. This year, Wake Forest University and University of Kansas Medical Center battled local San Francisco institutions UCSF and Stanford University for more than an hour in a Jeopardy-style format. After “FINAL IDBugBowl,” which all participants wagered on their answer to the question, “Oculomasticatory mylorythmia is pathognomonic for this infectious disease,” Stanford University was declared the winner. Congratulations to them and all the participants!
If you know which infectious disease is associated with “Oculomasticatory mylorythmia,” please answer in the comment section of this blog. Next year’s IDWeek will be held in Washington DC on October 2-6, 2019.