HHV-6 reactivation is one of the most common causes (in 30-70% of patients) of encephalitis in allo-SCT. It is a ubiquitous viral infection that remains latent and can reactivate after transplant.
Risk factors: HLA mismatch, T-cell depletion therapy, treatment with glucocorticoids, and the use of cord blood as a source of stem cells; 90% of cases of HHV-6 reactivation occur in patients who with cord-blood transplants.
Encephalitis presents as subacute confusion, but some may have a more progressive course. Anterograde amnesia, personality changes, irritability and seizures. SIADH is common.
CSF analysis shows mild lymphocytic pleocytosis and protein elevation.
Treatment is based on in-vitro susceptibility testing and foscarnet is therapy of choice. Can add ganciclovir if not clinically improving. But need to monitor closely for side effects including bone marrow suppression and electrolyte derangement which can predispose to seizures. Alternative therapy is cidofovir, but watch out for nephrotoxicity. Duration is 3-6 weeks and you shouldn’t monitor PCR levels to shorten treatment duration.
Notes from: N Engl J Med 2018; 378:659-669
For most patients: Ampicillin/Sulbactam is sufficient for oral aerobe/anaerobic coverage
For penicillin allergic patients: Clindamycin monotherapy covers oral aerobes/anaerobes
For hospital-acquired aspiration PNA: Coverage of aerobic bacteria, especially GPC and GNR are more important than anaerobes: Pip/Tazo or meropenem monotherapy
In patients with high risk factors for MRSA, can add an agent with MRSA activity but if MRSA is not detected, this agent should be discontinued
Meta-analysis found in vitro synergy. Especially in A baumanii. Mechanism unclear
Synergy testing can be done on isolate if available
Can not necessarily infer in vivo synergy (Beta-lactam/aminoglycoside synergy is demonstrated in vitro but NOT in vivo for example).
Systematic Review and Meta-Analysis of In Vitro Synergy of Polymyxins and Carbapenems. Antimicrobial Agents and Chemotherapy. October 2013 Volume 57 Number 10. p.5104 – 5111.
16 studies were included – significant heterogeneity, but of 2359 patients. Heterogeneity was assessed graphically and with a Q test. The Q test should only be used once in a data set to exclude outliers. The reference standard, we considered it to be of high quality if based on CT alone or when it consisted of a final diagnosis made by experts using an integrated synthesis of radiology and laboratory or microbiological data (or both).
The highest risk of bias stemmed from the flow of patients within each study because of an uneven application of the reference test (differential verification bias).
The dispersion of studies in the ROC plane suggests marked heterogeneity.
The 95% CI of the overall effect indicates a sensitivity of approximately 80% to 90% and a specificity of 70% to 90%.
Accuracy of Lung Ultrasonography in the Diagnosis of Pneumonia in Adults: Systematic Review and Meta-Analysis – Ana M. Llamas-Álvarez, MD; Eva M. Tenza-Lozano, MD; and Jaime Latour-Pérez, MD, PhD; . Chest 2017; 151(2):374-382
Baseline rates of treatment failure have varied in studies and rates have ranged from 8.5 to 17% in the best case scenarios to 43-75% in other studies. So even at baseline, we know that a significant number of patients will fail antibiotics and require surgery. Risk factors include diabetes mellitus, leukocytosis greater than 12.5, positive blood cultures, and C-reactive protein greater than 115. One risk factor increases failure rates for to 35.4%, two risk factors increases failure to 40.2%, and three or more risk factors increases failure rates to 76.9%.
So basically, most patients should ideally managed with surgery and barring that we should advocate for surgery in patients who have risk factors.
STOP-IT trial: In patients with intraabdominal infections WITH source control, outcomes were similar between fixed duration (4 days) vs. duration guided by clinical improvement – 2 days after the resolution of fever, leukocytosis, and ileus (mean 8 days). Both intention to treat and per-protocol analysis found no difference. However, the study was terminated early due to funding, and only enrolled half the intended patients.
N Engl J Med 2015;372:1996-2005
- Definition: pneumonia that occurs 48 hours or more after admission and did not appear to be incubating at the time of admission.
- HCAP Removed because many patients who met criteria were in fact not at increased risk for multi-drug resistant organisms, MDROs
- Recommended antibiotics: anti-pseudomonal +/- double pseudomonal coverage +/- MRSA coverage
- MRSA Risks: abx use IV abx in past 90 days, unit where prevalence of MRSA among S. aureus isolates is not known or >20%. No recommendations regarding use of MRSA swab to guide need for MRSA coverage.
- Non-invasive Sputum cultures recommended to guide therapy
- Duration: 7 days
- New CAP guidelines (to include patients from nursing homes) are pending.