This is a case series of 10 patients who had staphylococcal biofilm infections that were treated with adjuvant rifabutin therapy instead of rifampin therapy. In these cases, rifampin was contraindicated secondary to drug–drug interactions with the patients’ chronic medications. Rifabutin therapy was well tolerated with no side effects. As well, no patients had recurrence of their staphylococcal infections. This case series shows that rifabutin can be a beneficial adjuvant therapy in Staphylococcus biofilm infections when drug–drug interactions limit the use of rifampin.
We previously reported that flagellin-expressing Pseudomonas aeruginosa (Pa) provokes NEU1 sialidase-mediated MUC1 ectodomain (MUC1-ED) desialylation and MUC1-ED shedding from murine lungs in vivo. Here, we asked whether Pa in the lungs of patients with ventilator-associated pneumonia might also increase MUC1-ED shedding. The levels of MUC1-ED and Pa-expressed flagellin were dramatically elevated in bronchoalveolar lavage fluid (BALF) harvested from Pa-infected patients, and each flagellin level, in turn, predicted MUC1-ED shedding in the same patient. Desialylated MUC1-ED was only detected in BALF of Pa-infected patients. Clinical Pa strains increased MUC1-ED shedding from cultured human alveolar epithelia, and FlaA and FlaB flagellin-expressing strains provoked comparable levels of MUC1-ED shedding. A flagellin-deficient isogenic mutant generated dramatically reduced MUC1-ED shedding compared with the flagellin-expressing wild-type strain, and purified FlaA and FlaB recapitulated the effect of intact bacteria. Pa:MUC1-ED complexes were detected in the supernatants of alveolar epithelia exposed to wild-type Pa, but not to the flagellin-deficient Pa strain. Finally, human recombinant MUC1-ED dose-dependently disrupted multiple flagellin-driven processes, including Pa motility, Pa biofilm formation, and Pa adhesion to human alveolar epithelia, while enhancing human neutrophil-mediated Pa phagocytosis. Therefore, shed desialylated MUC1-ED functions as a novel flagellin-targeting, Pa-responsive decoy receptor that participates in the host response to Pa at the airway epithelial surface.
BackgroundA few case reports have noted uncontrolled hyperglycemia in patients switched to dolutegravir. Several cohort studies have found increased weight gain among patients treated with integrase inhibitors (INSTI). We present clinical observations among 3 patients admitted to hospital for diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) while receiving INSTIs for the management of HIV.MethodsCase 1: A 44-year-old man with HIV and dyslipidemia presented with altered mental status and lethargy. A fingerstick glucose was >600 mg/dL. Chemistries revealed glucose of 1,600 mg/dL and an elevated β-hydroxybutyrate. HbA1c was 12.4%. His antiretroviral regimen consisted of cEVG/TAF/FTC for the last 3 years. Previous HbA1c levels were 5.7% and 6.2% (Figure 1). Case 2: A 55-year-old woman with HIV, hypertension, dyslipidemia, and obesity presented with polyuria and polydipsia. The blood glucose level was >1,200 mg/dL with an anion gap >30 and HbA1c of 15%. Previous HbA1c levels ranged between 5.6 and 5.8% (Figure 2). She had been taking ABC/FTC/DTG for 2 years.Case 3: A 64 yo man with a history of HIV, hypertension, and obesity presented with polyuria and polydipsia. The blood glucose level was 1,152 mg/dL with no anion gap and HbA1c of 13.4%. Six months before, he had been switched from a c/DRV- based ART regimen to ABC/FTC/DTG. Previous HbA1c levels ranged between 5.8% and 6.2% (Figure 3).ResultsDiscussion: In the first 2 patients, the presentation with acute onset DKA occurred more than a year after being on an INSTI-based regimen; however, the latter patient presented with HHS within 6 months of being switched to an INSTI-containing regimen. The mechanism of action of INSTIs causing weight gain or an association with hyperglycemia is still under investigation.ConclusionAlthough the temporal onset of DKA and HHS while receiving INSTIs was not precise, the possible association of INSTIs and their direct effects on insulin resistance and diabetes warrant additional attention from post-market data. Meanwhile, providers should monitor INSTI-treated patients closely, especially those with features of metabolic syndrome. Disclosures All authors: No reported disclosures.
Several cases of Multisystem Inflammatory Syndrome in Adults (MIS-A) have been reported in adults since June 2020 after COVID-19 was first reported in December 2019. It was initially reported in children as MIS-C with Kawasaki-like disease, but a similar condition has been well recognized in adults. Although Mycoplasma co-infection has been reported with COVID-19, to our knowledge, concomitant Mycoplasma pneumoniae infection has not been reported together with MIS-A. We present a case of MIS-A with concomitant M. pneumoniae infection. It is unclear if concomitant Mycoplasma infection resulted in increased severity of the patient’s illness or if it resulted in inciting the immune response in our patient who had recently recovered from COVID-19 infection. This case highlights the need to diagnose a patient with a typical presentation of MIS-A and any concomitant infection or illnesses.
Combination regimens of direct‐acting antiviral agents (DAAs) for chronic genotype 1 hepatitis C virus (HCV) infection given for 8 or 12 weeks have high cure rates. Shortened treatment durations that maintain high cure rates may lessen treatment barriers related to affordability and drug adherence. We enrolled 12 treatment‐naïve adults with chronic genotype 1 HCV infection without cirrhosis in a single‐center, open‐label trial to receive 2 weeks of the highly potent and selective non‐nucleoside inhibitor (NNI) CDI‐31244 concurrent with 6 weeks of sofosbuvir/velpatasvir. The main efficacy endpoints were sustained virologic response at 12 (SVR12) and 24 (SVR24) weeks after treatment completion. In all patients, plasma HCV RNA levels rapidly decreased during the first 2 days of treatment and were below the lower limit of quantification by the end of the 6‐week treatment period. Eight of 12 (67%) patients achieved both SVR12 and SVR24. Four patients had virological relapse at Week 10, 4 weeks after end of treatment. The most common adverse event was headache, occurring in five (42%) patients. Pharmacokinetic analysis showed no relevant drug interactions between CDI‐31244, sofosbuvir, and velpatasvir. In this pilot study of short‐duration combination therapy involving a novel NNI with a fixed‐combination DAA, 8 of 12 treatment‐naïve patients with chronic genotype 1 HCV infection without cirrhosis achieved virologic cure. Future trials might evaluate whether extending the NNI duration beyond 2 weeks with combination DAAs results in higher cure rates comparable with currently approved longer duration therapy.
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