#357 Hotcakes: Ultra-short Antibiotics for Pneumonia, Acetazolamide for CHF, Psilocybin for AUD, and Asymptomatic Kidney Stone Removal

September 28, 2022 | By Nora Taranto

Video

Find out if ultra-short course (two days) antibiotics work for pneumonia, if acetazolamide improves diuretic efficiency in acute decompensated heart failure, should we prescribe psilocybin (magic mushrooms) to treat alcohol use disorder, and if removal of asymptomatic kidney stones decreases the incidence of future events! Time to fill your plate with a fresh stack of hotcakes! Drs. Paul Williams (@PaulNWilliamz), Rahul Ganatra (@rbganatra), and Matt Watto (@doctorwatto) catch up on recent practice-changing articles and guidelines!

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Credits

• Written by: Nora Taranto MD; Rahul Ganatra MD, MPH; Paul Williams, MD, FACP, Matthew Watto MD, FACP
• Hosted by: Rahul Ganatra MD, MPH; Paul Williams, MD, FACP, Matthew Watto MD, FACP
• Cover Art: Matthew Watto MD, FACP
• Reviewer: Rahul Ganatral MD, MPH
• Technical Production: Pod Paste

CME Partner: VCU Health CE

Show Segments

• Intro, disclaimer
• Ultra-short Antibiotics for Pneumonia, 
• Acetazolamide for acute heart failure exacerbations, 
• Psilocybin for AUD,
• Asymptomatic Kidney Stone Removal
• Outro

Hotcakes

Deep dives on practice changing articles. 

Ultra-short antibiotics for pneumonia (Watto)

Klompas M, et al. Ultrashort course antibiotics for suspected pneumonia with preserved oxygenation. Clin Infect Dis. 2022 Jul 27:ciac616. doi: 10.1093/cid/ciac616. Epub ahead of print. PMID: 35883250.

Question: Does mortality or time to hospital discharge differ among hospitalized patients >18 years old with oxygen sats >95% after early discontinuation (aka ultra-short course) of antibiotics for suspected pneumonia? 

Comparison: This was a retrospective cohort study involving a subset of nearly 40,000 patients treated for possible pneumonia at 4 hospitals in Massachusetts. About ten thousand patients with pneumonia had median oxygen sats >95%, and the authors propensity-matched 4,478 patients treated with antibiotics for 1-2 days vs 5-8 days (2,239 patients per group). 

Results: As expected, patients in the ultra-short (1-2 days) group received 1.3 days of antibiotics vs 6.2 days of antibiotics in the comparator group (that is, they had more antibiotic-free days). There was no difference in mortality in the ultra-short group, and length of stay was less by 0.5 days (6.1 vs 6.6 days; HR 1.13 [95% CI, 1.07-1.19]). Thirty-day readmissions, 30-day mortality, and 90-day C. difficile infections did not differ between groups. 

Limitations: It is likely that patients treated for 1-2 days (vs 5-8 days) were less sick and the diagnosis of pneumonia was less certain. Residual confounding, or differences between groups not captured by propensity matching, could account for these results. Check out the scathing commentary on the journal site about the lack of imaging data on patients included in this study (https://doi.org/10.1093/cid/ciac616).

Bottom line: In this retrospective cohort study of patients with suspected pneumonia and oxygen saturation >95%, ultra-short treatment with antibiotics was not associated with worse outcomes. Randomized trials are warranted to confirm these results. 

Hotcakes rating:  3.5

Additional Reading: 

Dinh A, et al. Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards. Lancet. 2021. PMID: 33773631.

Hot Takes

Brief discussion of recent articles, medical news, guidelines

Removal of small asymptomatic kidney stones, and incidence of relapse (Nora via Watto)

Sorensen MD, Harper JD, Borofsky MS, et al. Removal of small, asymptomatic kidney stones and incidence of relapse. N Engl J Med. 2022;387(6):506-513. 

Question: Does the endoscopic removal of small (<6 mm), asymptomatic renal or ureteral stones reduce relapse? 

Comparison:  This multicenter, randomized controlled trial included 73 patients who had primary, “culprit” stones removed via percutaneous nephrolithotomy or ureteroscopy and also had additional, small asymptomatic stones present on imaging. Patients were randomized 1:1 to removal of additional stones by ureteroscopy at the time of primary stone removal or usual care (without stone removal). These stones were located in the contralateral kidney, or in either kidney in the case of a primary ureteral stone. The primary outcome was relapse, defined by future emergency department visits for a kidney stone on the side of the original stone, subsequent surgical stone removal on that side, or growth of secondary stones. Secondary outcomes were surgical time, ED visits within 2 weeks, and stone passage or new stone development. 

Results:  After a mean of 4.2 years of follow-up, the treatment group had a longer time to first relapse than the control group (1,632 versus 934 days, p<0.001), with an 82% lower relative risk of relapse in the treatment group (HR 0.18, 95% CI 0.07-0.44).  Six (16%) of 38 patients in the treatment group had a relapse, compared with 22 (63%) of 35 patients in the control group. Comparable numbers (5 vs 4) had ED visits within 2 weeks of the surgery, all related to stent pain. Treatment added just over 25 minutes to the surgery time. 

Limitations: Surgeons decided on the method of stone removal. Patients with known systemic disease (which isn’t defined) and anatomic kidney disorders were excluded from this study, and the number of patients screened for enrollment was not reported, making selection bias difficult to gauge. 

Bottom Line: In this small randomized control trial, removal of secondary stones at the time of endoscopic removal of symptomatic stones significantly reduced the risk of future kidney-stone related ED visits and the requirement for repeat procedures. 

Hotcakes rating:  3

Additional Reading:  

Goldfarb DS. Preemptive removal of small, asymptomatic kidney stones. N Engl J Med. 2022;387(6):562-563. 

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use DisorderA Randomized Clinical Trial (Paul)

Bogenschutz MP, Ross S, Bhatt S, et al. Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. Published online August 24, 2022.

Question: Does the administration of high-dose psilocybin reduce the percentage of heavy drinking days in patients with AUD undergoing psychotherapy?

Comparison: This was a double-blind randomized clinical trial in which patients received 12 weeks of psychotherapy and were randomized to receive psilocybin or diphenhydramine during sessions at week 4 and week 8. Patients recruited were aged 25 to 65, had a diagnosis of alcohol dependence by DSM-IV criteria, and had at least 4 heavy drinking days in the 30 days prior to screening. Exclusion criteria included major psychiatric or drug use disorders, any hallucinogen use in the past year, or more than 25 lifetime uses, or current treatment of AUD.  The participants were recruited using advertisements in local media.

Dosing of the psilocybin was weight-based (25 mg/70 Kg) for the first session, and the dose was increased for the second session if patients scored beneath a certain threshold on the Pahnke-Richards Mystical Experience Questionnaire. The control medication was diphenhydramine 50 mg at the first session and 100 mg at the second session. The medications were given in the morning, and the participants stayed in the session room with trained therapists for at least 8 hours. They were encouraged to lie on a couch wearing eye shades, and to listen to a standardized playlist of music through headphones.

The primary outcome was percentage of heavy drinking days (5 or more drinks in a day for men, 4 or more for women) during weeks 5-32. Secondary outcomes included mean drinks per day and percentage of drinking days. Alcohol use was assessed using the timeline followback method, as well as testing hair and nails at week 24 for ethylglucuronide. The Short Index of Problems (SIP-2r) was used to assess drinking-related problems at baseline, and at weeks 12, 24, and 36.

Results: Substantial decreases in the percentage of heavy drinking days, percentage of drinking days, and drinks per day occurred in both groups between screening and week 4. Percentage of heavy drinking days during the total 32 week period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group (mean difference, 13.9%, 95% CI, 3.0-24.7, P=0.01). The mean number of drinks per day was also lower in the study group.

Limitations: Blinding was not possible: in an integrity of blinding analysis, 93.6% of patients were able to correctly guess their treatment assignment at the first session, and 94.7% guessed correctly in the second session. The numbers were similar for the study therapists.

Bottom line: Psilocybin plus psychotherapy resulted in a marked reduction in heavy alcohol use over and above what was seen in active psychotherapy plus placebo.  To my mind, the major limitation is the inability to effectively blind participants to their treatment.  Additionally, this is a resource-intensive intervention that may not be ready for prime time given our inability to provide medications we already know to be effective.

Rating: 3 savory mushroom hotcakes

Acetazolamide in acute decompensated heart failure with volume overload (Rahul) 

Mullens W, Dauw J, Martens P, et al. Acetazolamide in acute decompensated heart failure with volume overload. New England Journal of Medicine. Published online August 26, 2022.

Question: Does acetazolamide, when added to usual care (loop diuretics) among patients admitted to the hospital with acute decompensated congestive heart failure (ADCHF), increase the incidence of successful decongestion by day 3?

• Successful decongestion: The absence of signs of volume overload (other than trace edema) as assessed by a cardiologist by day 3 after randomization. 
• Secondary outcomes included mortality, readmissions, and adverse events.

Comparison: This RCT was conducted at 27 centers in Belgium and included 519 patients (out of 2,915 screened). Patients all had to be hospitalized with ADCHF, and have at least one sign of volume overload (peripheral edema, ascites, or pleural effusion – note this did NOT include JVD), NT pro BNP > 1000 or BNP >250, had to be on oral furosemide equivalent of >40 mg QD for >1 month, could not be taking acetazolamide or an SGLT2i, or have stage 5 CKD. Patients were randomized in a 1:1 fashion to receive acetazolamide 500 mg IV daily or placebo, plus IV diuretics in a total daily amount corresponding to twice 2x the patient’s home dose. The mean age in the high 70s, and almost everyone was white. The baseline congestion score was 4/10 in both groups, almost all patients had edema, about half had pleural effusions. They were pretty sick: 30% had NYHA class 4 CHF, and 80% of patients in both groups had CKD. 

Results: Successful decongestion by day 3 occurred in 42.2% of patients randomized to acetazolamide, compared with 30.5% of patients randomized to placebo. This corresponds to an absolute difference of 11.7%, or a NNT of 9 patients over three days. The relative risk for decongestion from acetazolamide was 1.46 (95% CI, 1.17-1.82). Of the important secondary endpoints, LOS was shorter by about a day, and more acetazolamide patients were decongested at discharge, but there were no differences in deaths or rehospitalization for heart failure at 3 months. Notably, there were no glaring safety signals.

Limitations: The assessment of decongestion relied on subjective measures of extravascular volume overload. It is not clear whether the results are due to acetazolamide per se, or just more effective diuresis (patients randomized to acetazolamide had a cumulative urine output 0.5 L greater than patients randomized to placebo). In addition, all patients were white, so replication in other populations will be important.

Bottom line: This was a positive study. Looking for sources of chance or bias that could explain this has not turned up any glaring concerns. In fact, there is one source of chance that could bias towards a negative finding: that patients in the acetazolamide group required a higher cumulative dose of maintenance diuretics, a median of 60 mg furosemide daily vs 40 in the placebo group. This matters because the subgroup analyses reveal that acetazolamide might work better in less severe CHF. The magnitude of treatment effect was greater in people with LVEF >40%, people on <60 mg of furosemide daily, and people with a baseline congestion score of <4 on admission. So, if people in the acetazolamide group had worse heart failure reflected by needing more furosemide for maintenance, that could have made the primary outcome harder to achieve in that group and biased towards the null. That we saw a positive outcome despite this makes me feel even more confident in these results.

Hotcakes: 4  

Goals

Listeners will review recent practice-changing articles and medical news.

Learning objectives

After listening to this episode listeners will…  

1. Evaluate the use of tirzepatide for weight loss
2. Discuss how pharmacogenomics may improve antidepressant prescribing
3. Recognize seasonal trends in edema
4. Evaluate the use of nirmatrelvir for standard risk patients with COVID-19 infection

Disclosures

The Curbsiders report no relevant financial disclosures. 

Citation

Taranto NP, Ganatra RB, Williams PN, Watto MF. “#349 Hotcakes: Tirzepatide for weight loss, Personalized Antidepressants, Seasonal Edema, Nirmatrelvir for low-risk COVID-19”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date August 8, 2022.