An ongoing dialogue on HIV/AIDS, infectious diseases,
July 15th, 2018
On-Service Digest, July 2018 — with Special Section Just for Staph aureus
I’m currently on-service for the inpatient ID consult team, and this is July.
At a teaching hospital.
Here’s where some would play scary music. After all, the interns and fellows have just started! YIKES!
But no scary music for me — I love working with the July newbies.
Because whatever they lack in experience or efficiency, they more than make up for it with enthusiasm and motivation. They’re on that steep upward slope in the learning curve, and it’s fun to experience this firsthand.
Plus, there’s plenty of extra help around, and this year we hit the jackpot. In addition to an excellent first-year ID fellow, our team also has a resident with a distinguished ID pedigree and a medical student who has done ID research. If that weren’t enough, we also have a terrific ID PharmD who has his own keen residents.
Yes, we almost have enough people on rounds to field a decent softball team. We make quite the sight entering and leaving the elevator.
So what have we learned so far? Here are few items, ranging from obvious to obscure, inspired by a similar roundup last December.
- Here’s a terrific review for all clinicians of contemporary hepatitis C treatment. Sofosbuvir/velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (GLE/PIB) are the best options for initial therapy — pangenotypic, highly effective (>95% cures), well tolerated. Why choose anything else? Also, most patients need minimal monitoring — test for cure 12 weeks after treatment stops and monitor for re-infection if at ongoing risk. Provided they don’t have advanced liver disease (and referral to a hepatologist), that’s pretty much it!
- Compared to other candida species, Candida glabrata has both more azole and echinocandin resistance. This is particularly the case in transplant and oncology centers that use extensive antifungal prophylaxis. In vitro, Candida parapsilosis also shows reduced susceptibility to echinocandins, but the clinical significance of this finding is uncertain.
- TMP/SMX is likely fine for treatment of HIV-related cerebral toxoplasmosis. Small caveat — there has never been a fully powered comparative trial versus pyrimethamine/sulfadiazine. However, there is extensive international experience with TMP/SMX, plus increasing clinical use in the U.S. since Shkreli/Turing Pharmaceuticals raised the price of pyrimethamine from $13.50 to $750 per dose.
- Asplenia or hyposplenism is an important risk factor for severe babesiosis. Others risk factors include older age (>50, ugh), receipt of cancer chemotherapy, advanced HIV disease, and treatment with TNF blockers or rituximab. The last of these is a particularly bad player in persistent infection.
- Among patients with HIV, those with poor adherence often have little or no resistance. They don’t take enough of their medications to select for resistance. Further proof comes from several treatment-experienced trials of second-line therapy or beyond — baseline lack of resistance is associated with worse outcomes. Poor adherence carrying through to the second-line therapy explains this apparent paradox.
- Doxycycline reduces the risk of C. diff in hospitalized patients. This is one of many reasons it remains many ID doctor’s favorite antibiotic.
- In treatment-naive patients, dolutegravir plus lamivudine is non-inferior to dolutegravir plus TDF/FTC. Full results to be presented soon. This should mean that prices for HIV drugs come down — but it won’t be so simple, as explained in this excellent perspective from the NEJM.
- Carbamazepine and phenobarbital induce the metabolism of dolutegravir. For phenobarbital, the effect is likely to be substantial enough to make co-administration with dolutegravir contraindicated.
- Cefiderocol is an investigational cephalosporin with activity versus highly resistant gram negative infections. This includes many carbapenem-resistant isolates. It is a novel “siderophore cephalosporin,” meaning it’s transported through the outer membrane of bacteria through iron transporters (at least, I think that’s what it means).
- Obesity and diabetes are risk factors for invasive group B strep infections. This is now a more common pathogen in older adults than it is in newborns, a fact that surprises many medical students.
- Prednisone reduces the risk of immune reconstitution inflammatory syndrome (IRIS) in patients with HIV-related TB. IRIS was diagnosed in 47% of those in the placebo arm, versus 33% in prednisone arm. There was no difference in mortality.
- Corynebacterium striatum, commonly found as part of normal skin flora, can cause clinically significant infections. Vancomycin is the preferred initial therapy, as the organism is increasingly resistant to beta-lactams and quinolones. Other options include linezolid and daptomycin, based on susceptibility testing. Device, hardware and line-related infections are most commonly reported, along with respiratory tract infections in immunocompromised hosts and patients with COPD.
Special Staph aureus section — hey, this is inpatient ID, remember?
- Oxacillin is marginally better tolerated than nafcillin. Nafcillin has more renal-related adverse effects. However, cefazolin is better tolerated than both of them — but is it as active? Let the debate rage on.
- Penicillin-susceptible Staph aureus (PSSA) can be treated with penicillin. This presumes that the laboratory has definitively concluded it’s susceptible; since not all labs do this, however, the endocarditis guidelines recommend oxacillin or nafcillin for PSSA, even though penicillin is more active in vitro. (We tend to use penicillin at our hospital.)
- Adjunctive rifampin does not improve outcomes in Staph aureus bacteremia. Rifampin still has a role in prosthetic valve endocarditis, as it targets bacteria in biofilms which could induce late relapse. However, there is no need to use rifampin to clear the initial bacteremia, and giving it with a high burden of infection could select for resistance.
- There is an ongoing clinical trial comparing IV to oral antibiotics in uncomplicated Staph aureus bacteremia. Called SABATO (for “Staph aureus Bacteremia Treatment Options” — clever!), the trial will enroll patients after 5–7 days of IV therapy, randomizing them to continued IV versus oral TMP/SMX. If they have sulfa allergies, MSSA patients will get clindamycin, and MRSA patients will get linezolid.
- Mortality from Staph aureus pneumonia remains high. This is especially true when it’s a complication of influenza. And if it’s pneumonia due to MRSA, linezolid may be preferable to vancomycin.
- For surgical prophylaxis when concerned about MRSA, vancomycin alone isn’t enough. Vancomycin plus cefazolin is recommended. And count this as additional evidence that vancomycin has many weaknesses.
Hey, this list of medical/surgical specialties and classic rock songs left off Infectious Diseases!
Happy #ClassicRockDay July 13th y’all! Here’s a fun list of songs representing different medical specialties #medtwitter Feel free to add more to the setlist! #Physiatry is well represented with Walk This Way by @Aerosmith 🏃🏻♀️🏃🏾♂️🇺🇸🤘🏼@AAPMR @AAPhysiatrists 🎼 pic.twitter.com/12tLDQR90m
— Vinny Francio, MD (@VinnyFrancioMD) July 13, 2018
Here’s the obvious answer (with apologies to Peggy Lee and her very different song of the same name):
Hello,
Really appreciated your journal watch breakdown.
Minor quibble: probably would not pick daptomycin for destination therapy in device associated Corynebacterium striatum infections. Our group (https://www-ncbi-nlm-nih-gov.offcampus.lib.washington.edu/pubmed/26544621) and others (https://www-ncbi-nlm-nih-gov.offcampus.lib.washington.edu/pubmed/24973133) have reported rapid emergence of resistance in isolates that tested “susceptible” with resulting clinical failures.
thanks!
Will Hahn
Very interesting! What do you think of linezolid as a non-vancomycin alternative?
thank you,
Paul
Music in hospitals!
As soon as I saw the clinical trial name SABATO, “Mr. Roboto” by Styx popped into my head and now I can’t get rid of it! Argh! An earworm! Well, there are worse earworms to have. None of which I will list, as earworms are infectious, as we all know. Merely hearing the name of an earworm is enough to become infected. Any progress on treatment options for earworms? 🙂
But seriously, Paul. Thanks so much for these summaries, as always. I learn so much from them. And doxy is a favorite among us primary care folks, too.
Apologies to anyone who now has Mr. Roboto running through their head. Domo.
Thanks for kind words.
We have used linezolid during acute periods without failure and in our single-institution case series (https://www.ncbi.nlm.nih.gov/pubmed/27767926), no isolates tested “resistant.” This is similar to other institutions (https://www.ncbi.nlm.nih.gov/pubmed/29339389).
Linezolid should work but, as the old saying goes, “clinical experience is limited.” Our experience is that linezolid is relatively poorly tolerated over extended periods of time required for hardware associated infections. With LVAD infections (in particular) this can be quite problematic.
Appreciate the blog as always but I object to the absence of family medicine in the setlist
What’s the link between your resident and Dr. Nagami’s book? I haven’t read the book but just ordered it, looking forward to some fun reading.
That’s her Mom!
Paul
Many thanks for this insightful On-Service Digest, Dr. Sax
Here are some personal addition to the above:
1) TMP/SMX is likely fine for treatment of HIV-related cerebral toxoplasmosis.
I have been treating Cerebral Toxo with TMP/SMX for around 3 years now because of two reasons: first, many presentations are unable to take oral meds due to concomitant oral thrush and/or esophagitis and seizures, that leave the patient without the abbility to take the treatment orally; the second one is due to the shortage of pyrimethamine in my country (Argentina). Up to today, outcomes were very succesful but, as you mentioned, there aren´t studies of non-inferiority between these two regimens.
2) Oxacillin is marginally better tolerated than nafcillin
In Argentina, we don´t have anti-staphyloccocal drugs available, so we use cefazoline as the standard of care in MSSA bacteremia (although, we use 2 grs q8h). Very good outcomes, by the way and no side effects neither. And about susceptibility to Penicilin, there is a study that shows that 80% of Staph aureus (MSSA and MRSA) produce beta-lactamases, and our Micro Lab doesn´t test Penicilin, so we acually have no choice other than cafazolin or cefalotin, the later given 2grs q6h.
Also looking foward for that SABATO Study results, but just wondering why Linezolid instead of TMP/SMX. I have always had a “gut feeling” that 7 days of iv plus oral will suffice in certain patients.
Just sharing some of my personal experience.
And, about the song realted to ID: “Like a Virgin – Madonna” can be added; virgin of antibiotics, that is!
Best regards!
Peggy Lee sometimes comes in my mind when I do a consult for fever…
https://www.bing.com/videos/search?q=you+give+me+fever++youtube&view=detail&mid=238337A57F03E9AC0EE4238337A57F03E9AC0EE4&FORM=VIRE
Thank you for this excellent piece.
I can’t contribute anything meaningful to the ID topics but for music..
Hot Blooded – Foreigner
“Well, I’m hot blooded, check it and see
I got a fever of a hundred and three”