An ongoing dialogue on HIV/AIDS, infectious diseases,
December 13th, 2021
ID Learning Units from Inpatient ID Consults
Need a break from all-things COVID-19? Feeling OH-verwhelmed by OH-muh-kron?
(I guess that’s how some pronounce it … or AWE-mee-kron… or oh-MIKE-ron … or who knows. Two things for sure — there’s no “n” after the “m”, and it’s a drag regardless of how it’s pronounced.)
To cheer everyone up, here’s a palate cleanser of non-COVID-19 ID Learning Units from a stretch on the inpatient ID service earlier in the fall. I’ve been storing them up just for today.
Here are the criteria for inclusion:
- Has to be related to a case.
- Has to be posted each consecutive day. (Careful readers will note I missed one so did two on one day. Mea culpa.)
- Has to have a reference.
- Has to be interesting.
- Has to have no patient confidentiality issues.
And for this batch, it has to be a non-COVID-19 topic. Though some may find it hard to believe, there are other infectious diseases out there — in fact the entire field of ID existed before SARS-CoV-2 ever jumped its way to humans and started this dismal pandemic.
As always when on service, I’m very grateful to have worked with a couple of highly energetic and smart ID fellows, an ID pharmacy team (faculty and resident) who taught me something daily, plus a medical resident who seems destined (I hope) to be a great future ID doc.
Hooray for that!
Off we go, each with a bit of commentary about why they were selected:
#1:
Day #1: NADIA trial — after rx failure, DTG non-inferior to DRV/r when given with either TDF/3TC or ZDV/3TC, despite *extensive* NRTI resistance. Huge implications for management of both viremic and suppressed patients. https://t.co/Mjx6EWoH4J
— Paul Sax (@PaulSaxMD) October 13, 2021
NADIA is one of the most practice-changing studies in HIV medicine in a while — which ironically will be more relevant in clinical practice for those already suppressed than those with treatment failure, even though the latter is the study population.
Key question — can essentially all people with HIV on 3-class regimens or NRTIs plus boosted PIs due to resistance switch to tenofovir/FTC plus DTG? Or even simpler, to BIC/FTC/TAF? I think so, provided they have full susceptibility to INSTIs.
#2:
Day #2: Xpert MTB/RIF outperforms AFB smear in ruling out TB in low prevalence settings, with two negatives having a 100% neg predictive value. An important advance in hospital infection control. @annieluet https://t.co/zR5cxxTMQk pic.twitter.com/NEUY2I4XLN
— Paul Sax (@PaulSaxMD) October 14, 2021
The results of this study greatly expedite the tuberculosis rule-out, which in low-prevalence settings is done on many patients with an extremely low pre-test probability of TB. As always, no test is 100% perfect in the real-world setting, which means that for high pre-test probability cases, we might need to keep up precautions even with negative testing.
#3:
Day #3: For pts with recurrent cellulitis, this RCT showed that penicillin reduced the incidence of cellulitis from 37% to 22% over a median of 25 months of follow-up. NNT to prevent 1 episode of 5. Practice-changing study for many clinicians. https://t.co/b27R12pP3D
— Paul Sax (@PaulSaxMD) October 15, 2021
I find myself citing this study repeatedly, probably because there are so few clinical trials of long-term antibiotic use that so clearly demonstrate benefit. And don’t forget the compression stockings, another effective measure!
#4:
Day #4: Small comparative clinical trial found T/S as effective as sulfa-pyr for toxo encephalitis, and better tolerated. Results reinforced by observational data and clinical experience globally. Often we switch to T/S at d/c — what's your practice? https://t.co/6mI3yiCZxg pic.twitter.com/KObKFzabTJ
— Paul Sax (@PaulSaxMD) October 16, 2021
This is the only randomized trial comparing TMP/SMX to pyrimethamine plus sulfadiazine for HIV-related cerebral toxoplasmosis, and it’s woefully underpowered (a fancy way of saying, “too small”). But globally many more use TMP/SMX for this infection — it’s more readily available, less expensive, and much easer for patients to take.
Since it’s highly doubtful that there ever will be another controlled clinical trial, at what point do guidelines shift to recommend TMP/SMX over pyrimethamine-sulfa solely on the weight of clinical experience? I’d vote soon, since it’s not as if the pyrimethamine-sulfa strategy itself was ever subject to a controlled studies. (And no, I don’t know why this 1998 study was reprinted in December 2020.)
#5:
Day #5: The Staph intermedius group includes several coag pos staph spp that are the predominant cause of soft tissue infection in dogs — but can rarely also cause invasive disease in humans. Woof https://t.co/qCvwTlZcdI @NeilanAnne pic.twitter.com/wZ6aPGPKpY
— Paul Sax (@PaulSaxMD) October 17, 2021
Hi Louie! A self-indulgent post about a little known dog-related fact.
#6:
Day #6: Cefepime neurotoxicity is most common in older patients with renal dysfunction (heard that one before?), and should be considered especially in those with myoclonus. Don't forget dose adjustment in renal disease! https://t.co/Rl9Wcm6Gwd pic.twitter.com/JEbqlOBGqz
— Paul Sax (@PaulSaxMD) October 18, 2021
Anecdotal impression: Among hospital-based clinicians (hospitalists and medical residents), there is much greater awareness of this notable adverse effect of cefepime — especially with the decline in use of vancomycin plus piperacillin-tazobactam due to concerns about its renal toxicity.
#7:
Day #7: S maltophilia is intrinsically resistant to many agents (n.b. carbapenems), but often retains susceptibility to T/S, levo, ceftaz, mino. T/S usually listed as Rx of choice, but no comparative studies. Meta-analysis: FQ at least as good as T/S. https://t.co/4Rd48eNzDq pic.twitter.com/HH29KqOX0a
— Paul Sax (@PaulSaxMD) October 19, 2021
“Steno” is such a tough bug to treat, and TMP/SMX at high dose can’t be used for everyone. Spoiler alert — another good observational study on TMP/SMX vs levofloxacin about to be published soon in a journal near you.
#8:
Day #8: Cefiderocol enters bacterial cells using active iron transporters & is active against many MDR GNR. C/w best available Rx, cefiderocol similar to best therapy vs CRE, but w/ numerically more deaths — cause unclear. Chance due to small #'s? Other?https://t.co/s7pOmv0rb3 pic.twitter.com/kpenANJZsR
— Paul Sax (@PaulSaxMD) October 20, 2021
This is one of those inexplicable clinical trials, with an important outcome — deaths! — happening more in the experimental cefiderocol than the control arm, for reasons that still are not clear. (Reminds me of the early clinical trials of bedaquiline.) I suspect it’s because the heterogeneity of the patients with these infections is so huge that there’s the chance of death for multiple noninfectious reasons too, but I don’t know. For now, as we await more data, cefiderocol is increasingly used for treatment of highly resistant gram-negative infections in the hospital.
#9:
Day #9: How quickly can antibiotics turn blood cultures negative? Fast! The rate of pos blood cultures reduced by >50% just an hour after IV antibiotic Rx — but many will still be positive, so getting cultures in septic pts still useful. https://t.co/XOywNPd5Ob pic.twitter.com/xOP4mmI960
— Paul Sax (@PaulSaxMD) October 21, 2021
Reminder to emergency room, primary care, and urgent care clinicians everywhere — get blood cultures before starting antibiotics. Thank you very much, you’ve just made a lot of ID doctors very happy.
#10:
Day #10: Can we use cefazolin for treatment of central nervous system infections due to MSSA? Good concise summary of the data, pro and con, here. h/t @BWDionne https://t.co/VskwYvLi3Z pic.twitter.com/RJikvkJFrr
— Paul Sax (@PaulSaxMD) October 22, 2021
This particular question — can we use cefazolin over oxacillin or nafcillin for CNS infections due to MSSA — comes up all the time. The short answer is probably yes, with the bad reputation of cefazolin for this indication likely a carry-over from observations about another first-generation cephalosporin, cephalothin.
#11:
Day #11: In RCT of linezolid vs vanco for MRSA pneumonia, clinical response (PP analysis) was significantly higher with linezolid. Similar results in the ZEPHyR study (2013). Both had methodological issues, but data suggest it's as least as good. https://t.co/LXWc5m20op pic.twitter.com/2DNUkC6Gc8
— Paul Sax (@PaulSaxMD) October 23, 2021
Back when linezolid was a branded antimicrobial and cost a ton, many didn’t believe this company-sponsored clinical trial, discounting the results on various methodologic issues.
However, a second study found the same result (linezolid better than vancomycin), and hence this is one recommendation I frequently make when consulted on a case of MRSA pneumonia — switch the vancomycin to linezolid.
#12:
Day #12: Chemoprophylaxis is recommended for close contacts of patients with meningococcal infection. How about exposure to culture-positive respiratory secretions, e.g. from pneumonia or pharyngitis? CDC says no — interesting distinction. https://t.co/yrVwU6NSTZ pic.twitter.com/vpBAte42Dy
— Paul Sax (@PaulSaxMD) October 25, 2021
Since I don’t really understand this difference in recommendations for preventive therapy, allow me to quote Dr. Patrick Hickey: “Meningococcus is one of those infections for which every time there is a possible exposure physicians dutifully review the guidelines and then (more often than not) don’t follow them.” Agree!
#13:
Day #13: Impaired renal function is a risk factor linezolid-related thrombocytopenia. According to @BWDionne, we may one day see recommendations for reduced dosing (600 mg daily?) in patients with low eGFR. https://t.co/gYYygjmvXi pic.twitter.com/OQD0jNZo3p
— Paul Sax (@PaulSaxMD) October 26, 2021
More on linezolid! A reminder that impaired renal function is a risk factor for drug toxicity, which can be severe. Seems like dose reduction for this drug in some patients would be warranted, but is not now currently recommended.
#14:
Day #14: After suppression with boosted PI (bPI) plus NRTI as 2nd-line ART, maintenance Rx with bPI plus 3TC has high rates of success, even with M184V — better than bPI monoRx. One of many studies showing ongoing antiviral effect of 3TC even with M184V. https://t.co/kEVOaHLMHK pic.twitter.com/Cq30jbuBQq
— Paul Sax (@PaulSaxMD) October 26, 2021
Monotherapy studies with boosted PIs and dolutegravir have invariably failed despite their high resistance barrier, with more virologic rebound and development of resistance. As demonstrated in the NADIA trial (see #1, above), this can be overcome with just partial NRTI activity — which here in MOBIDIP is lamivudine despite the M184V mutation.
That’s a wrap! I’ll be on again over the holidays, will likely do the same.
Now enjoy this amazing visual (just a clip) of an extraordinarily beautiful piece — Un Sospiro (A Sigh), by Franz Liszt, played and displayed in a novel way. In dark times, it’s helpful to remember that human beings can do remarkable things.
https://twitter.com/YouTube/status/1350533338998693891?s=20
Plenty more where that come from!
Excellent! Please post more pearls in this format!
Re: cefiderocol, remember the hullabaloo about increased mortality with cefepime, back in 2010?
Thanks for the Lizst moment. How do you find these little gems every week? Do you have seven dwarfs out there mining the internet?
Hi Dr. Sax,
Well timed for you to reference a study about both linezolid vs vancoymcin and potential nephrotoxicity with linezolid. I think this might make an interesting blog post, what antibiotic do you prefer for MRSA coverage in the context of acute kidney injury, and when do you believe an ID consult is warranted. I currently have a relative at Beth Israel who presented with DKA and COVID pneumonia necessitating positive pressure ventilation. He was being covered with azithromycin, ceftriaxone, and vancomycin. During his first two days his creatinine rose from 1.0 to 2.1. At that time, it wasn’t known if it was pre-renal or intra-renal. I expressed concern about the vancomycin and requested ID and nephrology consults because that seemed a challenging clinical context, but the critical care service pushed back and didn’t order the consults believing his AKI was within their realm of expertise. His AKI was subsequently found to be ischemic acute tubular necrosis and he doesn’t have MRSA, but were my concerns about vanco, especially at troughs above 15, easily becoming toxic in the context of declining kidney function valid, and when should critical care specialists bring in ID for help with antibiotics in the context of AKI?
Looking for some reassurance in practice given NADIA results with this patient example. High-level resistance to all NRTIs and full susceptibility to INSTIs. Undetectable for the last 15 years with a current regimen of once daily dolutegravir, doravarine, and darunavir-cobi. Adherence is perfect. How would you feel about a simplification to BIC/FTC/TAF with close virologic follow up?