Successful Treatment of Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Patients With Immunodeficiency With Extended Nirmatrelvir/Ritonavir: Case Series.

Immunocompromised patients with B-cell deficiencies are at risk for prolonged symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We describe 4 patients treated for B-cell malignancies with B-cell-depleting therapies who developed persistent SARS-CoV-2 infection and had resolution of symptoms following an extended course of nirmatrelvir/ritonavir.

Invasive Aspergillosis: Epidemiology, Clinical Aspects, and Treatment.

Invasive aspergillosis remains an often fatal, difficult-to treat infection in immunocompromised patients. Patients not classically defined as immunocompromised, especially those in an intensive care unit setting, also develop invasive aspergillosis. Clinical clues suggesting angioinvasion and radiographic modalities, especially computed tomographic scans, combined with newer non-culture-based diagnostic techniques, have allowed earlier recognition of invasive aspergillosis. Although mortality remains high, it has greatly decreased over the past 15 years. Voriconazole has supplanted amphotericin B, with its various toxicities, as primary treatment for invasive aspergillosis. Combination therapy with voriconazole and an echinocandin for initial therapy, based on results from a recent controlled clinical trial, could become the standard of care in high-risk patients.

Severe Influenza in 33 US Hospitals, 2013-2014: Complications and Risk Factors for Death in 507 Patients.

BACKGROUND: Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013-2014 influenza season. Little is known about the epidemiology of severe influenza during this season. METHODS: A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes. RESULTS: A total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4-6.9], P=.006 and 50-64 years, 2.5 [1.3-4.9], P=.007; reference age 18-49 years), male sex (1.9 [1.1-3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9-37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2-1.4], P<.001). CONCLUSION: Risk factors for death among US patients with severe influenza during the 2013-2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.

Risk factors for piperacillin/tazobactam-resistant Gram-negative infection in hematology/oncology patients with febrile neutropenia.

PURPOSE: Febrile neutropenia (FN) is a life-threatening complication of cancer therapy, and initial ineffective therapy is associated with poor outcomes. Piperacillin/tazobactam (PTZ) is a commonly used empiric antibiotic for the treatment of FN, but resistance among Gram-negative pathogens is well described. We conducted a retrospective case-control study to identify risk factors for PTZ-resistant (PTZ-R) Gram-negative isolates. METHODS: Hematology/oncology patients with FN from November 2007 to November 2013 with a positive culture for Gram-negative bacilli were divided into two groups: PTZ-sensitive (PTZ-S) and PTZ-R. A multivariable model using logistic regression was constructed to identify risk factors for PTZ-R. RESULTS: A total of 171 patients were included (25 PTZ-R, 146 PTZ-S), yielding a 14.6 % resistance rate. Thirty-day all-cause mortality was significantly higher in the PTZ-R group (29 vs 11 %, P = 0.024). Multivariable analysis yielded intensive care unit (ICU) status (odds ratio (OR) 20.18; 95 % confidence interval (CI) 1.03-397.35; P = 0.048), antibiotics for > 14 days in the previous 90 days (OR 6.02; CI 1.17-30.93; P = 0.032), and respiratory source (OR 13.65; CI 1.14-163.57; P = 0.039) as significant risk factors for PTZ-R, and the receiver operating characteristic area under the curve of the model was 0.894. Among PTZ-R isolates, 88 % were sensitive to meropenem and 100 % were sensitive to amikacin. CONCLUSIONS: Given the high mortality rates in the PTZ-R group, a risk-factor-guided approach driven by this multivariable model may help identify patients that could benefit from amikacin combination therapy to help optimize empiric therapy in this setting.

Nocardia-induced granulocyte macrophage colony-stimulating factor is neutralized by autoantibodies in disseminated/extrapulmonary nocardiosis.

BACKGROUND: Nocardia species cause infections in both immunocompromised and otherwise immunocompetent patients, although the mechanisms defining susceptibility in the latter group are elusive. Anticytokine autoantibodies are an emerging cause of pathogen-specific susceptibility in previously healthy human immunodeficiency virus-uninfected adults, including anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies with cryptococcal meningitis. METHODS: Plasma from patients with disseminated/extrapulmonary nocardiosis and healthy controls was screened for anticytokine autoantibodies using a particle-based approach. Autoantibody function was assessed by intranuclear staining for GM-CSF-induced STAT5 phosphorylation in normal cells incubated with either patient or normal plasma. GM-CSF-mediated cellular activation by Nocardia was assessed by staining for intracellular cytokine production and intranuclear STAT5 phosphorylation. RESULTS: We identified neutralizing anti-GM-CSF autoantibodies in 5 of 7 patients studied with central nervous system nocardiosis and in no healthy controls (n = 14). GM-CSF production was induced by Nocardia in vitro, suggesting a causative role for anti-GM-CSF autoantibodies in Nocardia susceptibility and dissemination. CONCLUSIONS: In previously healthy adults with otherwise unexplained disseminated/extrapulmonary Nocardia infections, anti-GM-CSF autoantibodies should be considered. Their presence may suggest that these patients may be at risk for later development of pulmonary alveolar proteinosis or other opportunistic infections, and that patients may benefit from therapeutic GM-CSF administration.