Weekly Articles – 9/12/2021

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Liao X, Wang Y, He Z, et al. Three-month pulmonary function and radiological outcomes in COVID-19 survivors: a longitudinal patient cohort study. Open Forum Infect Dis. 2020;ofaa540. Published 2020 Nov 14. doi:10.1093/ofid/ofaa540

How does pulmonary function fare following COVID infection? This retrospective study 172 patients who were hospitalized with COVID and evaluated both CT and PFT findings 3 months following their initial admission. When looking at PFTs at 3 months post-COVID, there was no difference between those who had moderate or severe COVID.

Only 10 patients who had non-severe COVID and 1 patient who had severe COVID had abnormal PFTs at month 3. When looking at CTs, however, 85% still had some sort of abnormalities, usually fibrotic changes.

CT scores were higher in severe patients. I think the imaging findings are not terribly surprising, since these can lag behind the clinical picture. Further, there may be some sort of fibrinous organizing pneumonia going on post-Illness that is being caught on imaging. I think the PFTs are, however, encouraging. 

Thompson MG, Stenehjem E, Grannis S, Ball SW, Naleway AL, Ong TC, DeSilva MB, Natarajan K, Bozio CH, Lewis N, Dascomb K, Dixon BE, Birch RJ, Irving SA, Rao S, Kharbanda E, Han J, Reynolds S, Goddard K, Grisel N, Fadel WF, Levy ME, Ferdinands J, Fireman B, Arndorfer J, Valvi NR, Rowley EA, Patel P, Zerbo O, Griggs EP, Porter RM, Demarco M, Blanton L, Steffens A, Zhuang Y, Olson N, Barron M, Shifflett P, Schrag SJ, Verani JR, Fry A, Gaglani M, Azziz-Baumgartner E, Klein NP. Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings. N Engl J Med. 2021 Sep 8. doi: 10.1056/NEJMoa2110362. Epub ahead of print. PMID: 34496194.

How much do vaccines help with regards to hospitalization, ICU admission, and ER/urgent care visits? This retrospective study used the VISION Network cohort to evaluate adults >50yo in terms of COVID-19 vaccine efficacy with respect to hospitalization, ICU admission, and emergency/urgent care visits for those who had lab-confirmed COVID-19. The authors used a test-negative design and propensity-for-vaccination scores to evaluate overall efficacy. A total of 103,199 hospitalizations, of which 64,400 occurred after age-specific vaccine eligibility, were evaluated. 41552 hospitalizations and 21522 ED/urgent care visits were evaluated, of which 4321 patients had confirmed COVID. Overall, mRNA vaccinations had high efficacy when looking at hospitalization, whether it was the Pfizer or the Moderna vaccine. This held true for both ICU admissions and ED/urgent care visits.

Not surprisingly, 2 vaccines were better than one (here, the authors defined partial 2 dose vaccines as those who received the second dose but presented less than 14 days after their second shot). Seriously, get your shots!

Zauche LH, Wallace B, Smoots AN, Olson CK, Oduyebo T, Kim SY, Peterson EE, Ju J, Beauregard J, Wilcox AJ, Rose CE, Meaney-Delman D, Ellington SR. Receipt of mRNA COVID-19 vaccines preconception and during pregnancy and risk of self-reported spontaneous abortions, CDC v-safe COVID-19 Vaccine Pregnancy Registry 2020-21. Res Sq [Preprint]. 2021 Aug 9:rs.3.rs-798175. doi: 10.21203/rs.3.rs-798175/v1. PMID: 34401872; PMCID: PMC8366802.

And do shots affect pregnancy?  This brief communication evaluated the risk of spontaneous abortion in patients who had reciefved at least one dose of any of the mRNA vaccines before conception or before 20 weeks of gestation. The risk of spontaneous abortion was compared with data of risk of spontaneous abortion according to maternal age group. 2022 patients were evaluated, of which 165 reported spontaneous abortion less than 20 weeks of gestation. The overall risk was 14.1% in the primary analysis and 12.89% in the direct maternal age-standardization to reference population. Comparing with the upper and lower limits of previous data from the authors, the risk was within the expected range:

Ong SWX, Chiew CJ, Ang LW, Mak TM, Cui L, Toh MPHS, Lim YD, Lee PH, Lee TH, Chia PY, Maurer-Stroh S, Lin RTP, Leo YS, Lee VJ, Lye DC, Young BE. Clinical and virological features of SARS-CoV-2 variants of concern: a retrospective cohort study comparing B.1.1.7 (Alpha), B.1.315 (Beta), and B.1.617.2 (Delta). Clin Infect Dis. 2021 Aug 23:ciab721. doi: 10.1093/cid/ciab721. Epub ahead of print. PMID: 34423834.

This retrospective study used a national cohort dataset to evaluate the outcome of patients infected with several variants of interest (B.1.1.7 aka alpha, B.1.351 aka Beta, and B.1.617.2 aka Delta). These patients were compared to 846 patients who had the wild-type virus. Primary endpoint was the development of severe COVID-19 based on hypoxia requiring supplemental oxygen, ICU admission, and/or death (it shoudl be noted the study also evaluated a smaller cohort, but I’ll be focusing on the national cohort). 2930 patients were reported, of which 976 had sequences available. Delta was the most common variant seen (48%), followed by alpha (20%), and beta (18%). After adjusting for age and sex in multivariate logistic regression model, B.1.617.2 (delta) was associated with increased disease severity, ICU admission, or death compared to non-VOC cases (aOR 4.9, 95% CI 1.43-30.78).

The Delta variant has also been associated with higher odds of pneumonia (aOR 1.88, 95% CI 0.95-3.76), as well as higher odds of severe infection (aOR 3.02, 95% CI 1.41-6.32). 

Those with the delta variant also had longer duration of shedding, based on PCR positivity:

So it may seem that the delta variant is not only more infectious, but more likely to cause severe cases. Have I mentioned to get the vaccines?

Pericàs JM, Hernández-Meneses M, Muñoz P, Martínez-Sellés M, Lvarez-Uria AÁ, de Alarcón A, Gutiérrez-Carretero E, Goenaga MA, Zarauza MJ, Falces C, Rodríguez-Esteban MÁ, Hidalgo-Tenorio C, Hernández-Cabrera M, Miró JM; Spanish Collaboration on Endocarditis—Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España (GAMES). Characteristics and outcome of acute heart failure in infective endocarditis: focus on cardiogenic shock. Clin Infect Dis. 2021 Feb 9:ciab098. doi: 10.1093/cid/ciab098. Epub ahead of print. PMID: 33560404.

This was a multicenter, prospective observational Spanish cohort that attempted to evaluate the outcome of acute heart failure in patients with endocarditis. Outcomes evaluated included the development of cardiogenic shock during infective endocarditis, in-hospital mortality, 1 year mortality, and relapses. Multivariate logistic and Cox regression analysis were used to figure out predictors of mortality, and propensity score analysis was used to adjust  for confounding variables. A total of 4856 patients were evaluated, of which 1652 had acute heart failure and 244 had cardiogenic shock. Patients who presented with both IE and acute heart failure tended to be older and have a higher NYHA classification on presentation; further those with any sort of heart failure also were more likely to have native valve and mitral involvement  compared to those who did not have heart failure. A few interesting things to note was that most of the patients presenting with cardiogenic shock were more likely to have CoNS as opposed to strep or staph:

Further, the rate of CNS  or other major emboli was similar between groups, though those without heart failure tended to have more pulmonary emboli. Not surprisingly, however, those with cardiogenic shock had more cardiac-related complication, including heart blocks and arrhythmias:

Survival was lower in those with cardiogenic shock. Multivariate analysis found that aortic or mitral regurgitation, LVEF <60%, heart block, acute renal failure, or arrhythmias were associated with cardiogenic shock:

Staph aureus and arrhythmias were also associated with both higher in-hospital and one year mortality. The most notably thing was that the highest risk for mortality was the lack of cardiac surgery, despite an indication to do one:

While I am a bit surprised that Staph was not the most common bug isolated from those who had cardiogenic shock, most of the findings are no-brainers. The biggest take-away, I think, is that mortality is ridiculously high in those who warrant surgical intervention for endocarditis. The decision to operate is on a case-by-case basis, but I think this would have people strongly consider surgical options if they indeed are available. 

Vollmer NJ, Rivera CG, Stevens RW, Oravec CP, Mara KC, Suh GA, Osmon DR, Beam EN, Abdel MP, Virk A. Safety and Tolerability of Fluoroquinolones in Patients with Staphylococcal Periprosthetic Joint Infections. Clin Infect Dis. 2021 Feb 19:ciab145. doi: 10.1093/cid/ciab145. Epub ahead of print. PMID: 33606003.

Ah my good friends, the quinolones. This was a single-center retrospective study that evaluated the unplanned FQ discontinuation in patients who received them for staphylococcal prosthetic joint infection post-total knee or total hip replacement. Those who underwent a DAIR approach (debridement and implant retention) were evaluated. 156 patients were included, of which 57.7% received a FQ-based regimen with rifamycin. Most of the FQs written for were levofloxacin (98%), while minocycline, cefadroxil, doxycycline, and TMP-SMX made up the bulk of the non-quinolone regimens. The rate of discontinuation was 36% in the FQ cohort compared to 3% in the non-FQ cohort, which was higher in the knee arthroplasty (42%) compared to hip arthroplasty (28%). 58 adverse events were reported in 46 patients that stopped FQ, with 9 reporting tendinopathy:

FQs are great antibiotics, don’t get me wrong, but I think we need to be vigilant about their use and reserved them for hard to treat infections (which, to be honest, I think staphylococcal prosthetic joint infection is a warranted indication). 

Cresswell FV, Meya DB, Kagimu E, Grint D, Te Brake L, Kasibante J, Martyn E, Rutakingirwa M, Quinn CM, Okirwoth M, Tugume L, Ssembambulidde K, Musubire AK, Bangdiwala AS, Buzibye A, Muzoora C, Svensson EM, Aarnoutse R, Elliott AM, Boulware DR. High-dose oral and intravenous rifampicin for the treatment of tuberculous meningitis in predominantly HIV-positive Ugandan adults: a phase II open-label randomised controlled trial. Clin Infect Dis. 2021 Mar 8;73(5):876–84. doi: 10.1093/cid/ciab162. Epub ahead of print. PMID: 33693537; PMCID: PMC8423465.

This is more of a proof-of-concept study on high dose rifampicin for tuberculous meningitis. African patients who were suspected or confirmed to have tuberculous meningitis were enrolled in a randomized trial that evaluate the use of IV-20 (IV rifampicin 20mg/kg/day) along with standard therapy, PO-35 (PO rifampicin 35mg/kg/day) along with standard therapy, and standard of care RIPE. Those who were in the IV-20 arm were able to receive PO-35 after 14 days of IV therapy. Primary endpoints were pharmacokinetic parameters, performed on day 2 pre-dose as well as day 14. 61 patients were included, with 92% having being co-infected with HIV. There were a few differences between groups, mostly in terms of CSF parameters with the opening pressure in the control group being lower than the other two groups, and WBC being higher in the IV-20 arm. Not surprisingly, the AUC24, Cmax, CCSF were higher in the IV-20 and PO-35 cohort:

More importantly, however, the rate of grade 3, 4, or 5 adverse events was not statistically different between the three groups. While underpowered for this, there was no difference in survival between groups:

I think this is an interesting one going forward. The amount of drug that gets into the CSF under the best of circumstances is small, so this would suggest that the dose of Rifampicin can be increased without much difference in adverse events. How this pharmacodynamic result translates into clinical practice remains to be seen, as the mortality rate in this cohort was pretty much the same between the three groups (though HIV co-infection may confound the results, considering the population evaluated here which tends to have a high rate of HIV infection, I think many studies will have to take that into account). 

Karmarkar EN, O’Donnell K, Prestel C, Forsberg K, Gade L, Jain S, Schan D, Chow N, McDermott D, Rossow J, Toda M, Ruiz R, Hun S, Dale JL, Gross A, Maruca T, Glowicz J, Brooks R, Bagheri H, Nelson T, Gualandi N, Khwaja Z, Horwich-Scholefield S, Jacobs J, Cheung M, Walters M, Jacobs-Slifka K, Stone ND, Mikhail L, Chaturvedi S, Klein L, Vagnone PS, Schneider E, Berkow EL, Jackson BR, Vallabhaneni S, Zahn M, Epson E. Rapid Assessment and Containment of Candida auris Transmission in Postacute Care Settings-Orange County, California, 2019. Ann Intern Med. 2021 Sep 7. doi: 10.7326/M21-2013. Epub ahead of print. PMID: 34487450.

This study dealt with the epidemiology of C. auris in several nursing homes (including LTACHs) in California, specifically Orange County. A total of 44 patients were identified in 17 facilities, with a total of 182 patients being identified by serial point prevalence surveys and discharge testing. Of the total 182 who tested positive via screening, 14 had clinical cases (6 blood, 3 urine, 2 respiratory secretion, 2 abdominal abscess, 2 wounds) and all isolates had an MIC to fluconazole of at least 64, and demonstrating high MIC to voriconazole, but remaining fairly susceptible to micafungin:

Interestingly, hand hygiene in the initial 9 facilities were C. auris was identified was below 80%, while 5/9 facilities did not have a chart labeling system to identify patients who were colonized with MRDOs. 

This is more of an interesting epidemiological study of C. auris, which I have written about in detail in the past, though I find it odd any facility would have 11% hand hygiene observed adherence rates (seriously). 

Kouijzer IJE, van Leerdam EJ, Gompelman M, Tuinte RAM, Aarntzen EHJG, Berrevoets MAH, Maat I, Bleeker-Rovers CP, van Crevel R, Ten Oever J. Intravenous to Oral Switch in Complicated Staphylococcus aureus Bacteremia Without Endovascular Infection: A Retrospective Single-Center Cohort Study. Clin Infect Dis. 2021 Sep 7;73(5):895-898. doi: 10.1093/cid/ciab156. PMID: 33606007; PMCID: PMC8423458.

This was a retrospective study evaluating oral step down therapy for complicated staph aureus bacteremia compared to IV therapy. Patients were excluded if they had endocarditis or any endovascular infections, and negative PET CT. Primary outcome was relapse of SAB within 3 months after stopping antibiotic therapy. PO step down (with clindamycin 600mg TID) was performed after 14 days of IV therapy. 106 patients were included, with those who had prolonged IV therapy being more likely to have persistent fever and blood cultures, as well as being more likely to have vertebral osteomyelitis or pulmonary foci of infection. Three month mortality was not statistically different between the two groups, though there was a trend towards higher mortality in the IV group (13.3% vs 6.6%). There were no relapses in either group. Not surprisingly, hospital admission length was shorter in the PO step down group. I don’t think we’re quite ready to implement oral step down therapy for complicated staph aureus bacteremia quite yet, but one could argue that those who do not have certain characteristics (i.e. persistent bacteremia beyond 48 hours), could do well with an oral option. There is also the question of whether a strategy like this one would work without the need for PET scan (which can be terribly expensive). I am not a fan of clindamycin, but given the high bioavailability, I am not surprised the authors chose this antibiotic.

Thorlacius-Ussing L, Sandholdt H, Nissen J, Rasmussen J, Skov R, Frimodt-Møller N, Dahl Knudsen J, Østergaard C, Benfield T. Comparable Outcomes of Short-Course and Prolonged-Course Therapy in Selected Cases of Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Pooled Cohort Study. Clin Infect Dis. 2021 Sep 7;73(5):866-872. doi: 10.1093/cid/ciab201. PMID: 33677515.

More Staph! This study evaluated data from 3 cohorts to evaluate the risk of mortality in low-risk staph aureus bacteremia with either a short course therapy (6-10 days) or prolonged course therapy (11-16 days). Anyone with complicated SAB or IE or any possible foci of infection were excluded. Primary outcome was death from any cause within 90 days of antibiotic completion. 645 patients from cohort I, 219 patients from cohort II, and 141 patients from cohort III were included. Using inverse probability of treatment weighting, there was no different in mortality when comparing either strategy across all 3 cohorts and when pooling the data:

There was also no association with increased relapse with either strategy:

It should be noted that, given the retrospective nature of the study, it is likely these patients were fairly selected. Having said that, I think it is reassuring that a few days of antibiotic less do not impact major hard outcomes, which means less hospital days and less PICC requirements.

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