Enterobacteriaceae bacteremias among cancer patients: an observational cohort study

SummaryBackgroundEnterobacteriaceae bacteremia is a common complication in patients with neoplasm. The cancer itself, chemotherapy-induced immunosuppression, and other cancer-related procedures play a role as predisposing factors for this condition. However, despite the clear association between cancer and Enterobacteriaceae bacteremia, the distinctive clinical characteristics of patients with cancer presenting with Enterobacteriaceae bacteremia have not been well established.MethodsThe population studied was a prospective cohort of adult hospitalized patients with Enterobacteriaceae bacteremia in a tertiary care hospital. We compared the clinical variables and microbiological features between patients with an underlying neoplasm (n=203) and those without (n=259). STATA software was used for statistical association analysis.ResultsIn a bivariate analysis, older age, prior exposure to aminopenicillins, fewer days of symptoms, biliary source of bacteremia, greater severity of APACHE II score, lower white blood cell and platelet counts, and the presence of Klebsiella pneumoniae were more common in the neoplasm group. In a multivariable analysis, K. pneumoniae bacteremia (odds ratio (OR) 6.13, 95% confidence interval (CI) 1.65–22.71; p=0.007), APACHE II score (OR 1.18, 95% CI 1.05–1.34; p=0.007), and exposure to aminopenicillins (OR 28.84, 95% CI 1.94–429.3; p=0.015) were associated with neoplasm. K. pneumoniae bacteremia was more commonly present in patients with lung and gastrointestinal cancers.ConclusionsWe have confirmed the association of K. pneumoniae bacteremia with underlying neoplastic disease, especially with gastrointestinal malignancies, which may allow stratification for initial empiric antibiotic therapy in this subset of patients. Prior exposure to aminopenicillins in the neoplasm group might contribute to this finding

Combination Antifungal Therapy in the Treatment of Scedosporium apiospermum Central Nervous System Infections

Treatment of Scedosporium apiospermum central nervous system (CNS) infection typically consists of an azole in combination with surgical debridement. This approach requires prolonged treatment and carries a high associated mortality. We present two cases of the successful treatment of S. apiospermum CNS infections with the combination of voriconazole and terbinafine

Case Report Combination Antifungal Therapy in the Treatment of Scedosporium apiospermum Central Nervous System Infections

Treatment of Scedosporium apiospermum central nervous system (CNS) infection typically consists of an azole in combination with surgical debridement. This approach requires prolonged treatment and carries a high associated mortality. We present two cases of the successful treatment of S. apiospermum CNS infections with the combination of voriconazole and terbinafine. Case Reports Case 1. An 81-year-old Hispanic woman with a past medical history significant for hypertension, diabetes mellitus, hypothyroidism, and chronic kidney disease presented with symptoms of sinusitis, including facial pain, nasal congestion, and rhinorrhea. The sinusitis was later complicated by the development of left orbital cellulitis. The patient underwent a functional endoscopic sinus surgery (FESS) without evidence of gross infection and was treated with oral levofloxacin. Three weeks later, her orbital cellulitis resolved; however, she developed nausea, vomiting, headaches, left vision loss, diplopia, and local pain. Her eye exam was significant for intact extraocular movements, no nystagmus, and a positive afferent pupillary defect. No periorbital edema or erythema was observed. Visual acuity for her right eye was 20/60 and for her left eye was 20/100. Her basic laboratory results were normal. She was diagnosed with a left orbital complex syndrome with optic neuropathy and underwent another FESS with sinusotomy and debridement. The patient was briefly placed on intravenous (IV) steroids, and she was discharged home on an oral prednisone taper and levofloxacin. However, the patient was readmitted 10 days later with worsening vision loss on the left; she was then only able to perceive light. The intraoperative cultures from her last FESS grew a moderate amount of mold, which was subsequently identified as Scedosporium apiospermum based on its characteristic macroscopic morphology and conidiation. Susceptibility testing of the isolate revealed a voriconazole MIC of 0.5 ug/mL. An orbital MRI revealed mildly elevated signal within the intraorbital segment of the left optic nerve, mild inflammatory changes surrounding the optic nerve sheath complex and the orbital apex, and very mild asymmetric prominence of the left extraocular muscles concerning for myositis Case 2. A 64-year-old White man with a previous diagnosis of eosinophilic pneumonia, which had been treated with high-dose steroids, cyclophosphamide, and mycophenolic acid, presented with subacute symptoms of headaches, fevers, aphasia, and ataxia. He was diagnosed with meningitis, cerebritis, and ventriculitis based on an elevated cell count in his cerebral spinal fluid (CSF) and consistent imaging; however, the etiology was unclear. He was treated with antibacterial therapy, including a 10-day course of vancomycin, cefepime, and ampicillin, with partial resolution of his symptoms. He had a negative infectious workup including a negative brain biopsy, as well as, a normal cerebral angiogram. A CT scan of the head demonstrated hydrocephalus, and he had an external ventricular drain placed. A month later, his mental status worsened. At that time, his vital signs were normal and his neurologic exam was notable for mild confusion. Cranial nerves II through XII were intact with the exception of slow saccades, but no nystagmus was present. Laboratory studies were remarkable for a slightly elevated white blood cell count (WBC) of 12.2 × 10 3 /uL (normal range: 4.5-11.0 × 10 3 /uL) and a decreased hematocrit (Hct) of 29.1% (normal range: 42-54%). A repeat evaluation of his CSF showed 326 WBC (normal range: 0-5 × 10 6 /L) with 83% neutrophils (normal range: 0-6%). His CSF protein was 113 mg/dL (normal range: 15-45 mg/dL) and glucose was 54 mg/dL (normal range: 40-80 mg/dL). Gram stain and bacterial cultures were negative. An extensive infectious workup was negative including, CSF AFB smear and culture, serum and CSF cryptococcal antigen, Toxoplasma gondii antibody, Parvovirus B19 antibody, CSF VDRL, CSF and serum PCR for HHV-6, EBV, HSV-1/2, CMV, WNV, enterovirus, and JC virus. An MRI of his brain revealed ventriculomegaly, an increased halo surrounding the lateral ventricles, and debris within the ventricles with restricted diffusion and ependymal and subependymal enhancement Case Reports in Infectious Diseases 3 Discussion Scedosporium apiospermum, the anamorphic (asexual state) of Pseudallescheria boydii, is a ubiquitous organism with a worldwide distribution Predisposing factors for progressive fungal CNS infection in the first case we presented included advanced age, previous antibiotic and steroid exposure, the presence of diabetes mellitus and recent sinus instrumentation. As an alternative to terbinafine, an IV echinocandin could have been considered in combination with oral voriconazole in this case, but the likelihood of a prolonged, and possibly lifelong, treatment course made IV administration less feasible. The second patient had intense immunosuppressive therapy as his main predisposing factor for progressive fungal CNS infection. He clearly had a notable improvement with normalization of CSF cell counts and CSF sterilization while on combination antifungal therapy; however, due to his multiple comorbidities and a prolonged hospitalization, the infection relapsed and he died. Although successful reports of this antifungal combination have been described in the treatment of S. prolifican

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health