Background Fungal brain abscesses in immunocompetent patients are exceedingly rare. Cladophialophora bantiana is the most common cause of cerebral phaeohyphomycosis, a dematiaceous mold. Radiological presentation can mimic other disease states, with diagnosis through surgical aspiration and growth of melanized fungi in culture. Exposure is often unknown, with delayed presentation and diagnosis. Case presentation We present a case of cerebral phaeohyphomycosis in a 24-year-old with no underlying conditions or risk factors for disease. He developed upper respiratory symptoms, fevers, and headaches over the course of 2 months. On admission, he underwent brain MRI which demonstrated three parietotemporal rim-enhancing lesions. Stereotactic aspiration revealed a dematiaceous mold on staining and the patient was treated with liposomal amphotericin B, 5-flucytosine, and posaconazole prior to culture confirmation. He ultimately required surgical excision of the brain abscesses and prolonged course of antifungal therapy, with clinical improvement. Conclusions Culture remains the gold standard for diagnosis of infection. Distinct microbiologic findings can aid in identification and guide antimicrobial therapy. While little guidance exists on treatment, patients have had favorable outcomes with surgery and combination antifungal therapy. In improving awareness, clinicians may accurately diagnose disease and initiate appropriate therapy in a more timely manner.
Background We report on a 56 year-old male with prolonged COVID-19 pneumonia who initially improved with dexamethasone and intubation but quickly decompensated. Clinical and radiologic features were consistent with VAP. Tracheal aspirate cultures grew carbapenem-resistant Enterobacter cloacae; meropenem (MEM) MIC was >8 ug/ml (resistant) while ceftazidime-avibactam (CZA) MIC was 2/4 ug/ml (susceptible). Lateral flow antigen assay detected a KPC enzyme. The patient was treated with CZA with steady improvement in respiratory function over the next two weeks. He then experienced an episode of tachycardia, prompting repeat culture. At this point the patient had been extubated: sputum culture grew KPC+ E. cloacae that now showed CZA-resistance (MIC >8/4 ug/ml) and paradoxical decrease in MEM MIC (4 ug/ml); meropenem-vaborbactam (< 2/8 ug/ml) was susceptible. Methods The pre- & post-CZA therapy E. cloacae isolates underwent whole genome sequencing using the Illumina 150bp paired end protocol; sequences were quality trimmed and compared. Results A point mutation in the plasmid blaKPC3 gene was identified in the post-CZA therapy isolate, an R163S mutation in the omega loop of the enzyme. ompC and ompF porin genes were analyzed to rule-out decreased influx as a mechanism for CZA-resistance: the pre- and post-CZA isolates had identical porin sequences. Conclusion This case highlights emerging mutations within KPC carbapenemases that lead to resistance to ‘last-line’ antimicrobials like CZA. The presumptive mechanism is increased KPC active site promiscuity due to increased omega loop flexibility, allowing increased ceftazidime binding and hydrolysis, and decreased avibactam binding and beta lactamase inhibition. Paradoxically, MEM susceptibility improves after such omega loop mutations, likely due to decreased active site binding affinity, a ‘seesaw’ effect between MEM and CZA. While authors have reported MEM MICs falling into the ‘susceptible’ category after an omega loop variant, these bacteria invariably develop secondary mutations leading to MEM treatment failure. Fortunately, given our patient’s improved respiratory status, the post-CZA E. cloacae isolate was felt to reflect colonization and the patient was discharged home without antimicrobial therapy. Disclosures Romney Humphries, PhD D(ABMM), Accelerate Diagnostics (Individual(s) Involved: Self): Consultant, Shareholder; IHMA (Individual(s) Involved: Self): Consultant; Melinta (Individual(s) Involved: Self): Consultant; Momentum (Individual(s) Involved: Self): Grant/Research Support; Pattern (Individual(s) Involved: Self): Consultant; QPex (Individual(s) Involved: Self): Consultant; ThermoFisher (Individual(s) Involved: Self): Consultant; Torus (Individual(s) Involved: Self): Consultant
Background Increased hospital length of stay (LOS) has been associated with increased rates of readmission, nosocomial infections, and cost during hospitalizations for orthopedic-related infections (HOIs). We hypothesized that Infectious Diseases (ID) consultation is associated with increased LOS for HOIs due to pending culture results delaying final recommendations. We assessed patient and care factors affecting LOS, including duration and timing of ID consultation, and identified process improvements to expedite discharge for HOIs. Methods We performed retrospective chart review of HOI admissions with ID consultation at Vanderbilt University Medical Center from May-August 2021. Differences in HOIs discharged <1 vs. >1 day after ID final recommendations were examined using Fisher’s exact, Chi-squared, and Wilcoxon rank sum testing. Clustering by patient for those with >1 admission was performed. We used multivariable and propensity score weighted negative binomial regression models to estimate adjusted rate ratios (aRR) and 95% confidence intervals (CI) for number of days followed by an ID consultant and LOS. Results HOIs discharged <1 day after ID final recommendations (69/105) had shorter median LOS (3 vs. 8 days, p< 0.001) (Figure 1), more oral-only antibiotic regimens (41% vs. 17%, p=0.003), and more frequent discharge to home (91% vs. 53%, p< 0.001). HOIs discharged >1 day after ID final recommendations were more likely to undergo multiple surgeries (28% vs. 12%, p=0.019) and peripherally inserted central catheter (PICC) placement (69% vs. 43%, p=0.013). For each additional day of ID consultation, there was associated increase in LOS (multivariable aRR 1.12, 95% CI 1.02-1.23; weighted aRR 1.12, 95% CI 0.99-1.26). Figure 1.Length of Stay after ID Final Recommendations Conclusion ID consultation is unlikely to be the primary barrier to hospital discharge but may be a marker for more complicated HOIs and increased LOS. Most patients with prolonged stays were discharged >1 day after ID final recommendations. Implementation of protocols to promote prompt ID consultation, streamline PICC placement, and coordinate outpatient intravenous antibiotics may accelerate transitions of care and discharges. Disclosures Milner B. Staub, MD, MPH, Gilead: Stocks/Bonds|Johnson & Johnson: Stocks/Bonds.
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