First-line management of necrotizing herpetic retinitis by prioritizing the investigation of immune status and prognostic factors for poor visual outcomes.

PURPOSE: To review management, treatment, and outcomes of patients with necrotizing herpetic retinitis (NHR) to propose an algorithm for first-line management of NHR. METHODS: Retrospective evaluation of a series of patients with NHR at our tertiary center between 2012 and 2021 using demographic, clinical, ophthalmologic, virological, therapeutic, and prognostic characteristics was performed. Patients were classified by NHR type: acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis. RESULTS: Forty-one patients with NHR were included: 59% with ARN, 7% with PORN, and 34% with CMV retinitis. All patients with CMV retinitis and PORN were immunocompromised versus 21% of patients with ARN. CMV infection was found in 14 (34%) patients, varicella zoster virus infection in 14 (34%) patients, herpes simplex virus type 2 infection in 8 (20%) and type 1 infection in 5 (12%) patients. Intravenous antiviral therapy was received by 98% of patients and intravitreal antiviral injections by 90% of patients. The overall complication rate during follow-up was 83% of eyes. Most frequent complications were retinal detachment (33% eyes) and retinal break (29% eyes). Prognostic factors for poor visual outcomes were pre-existing monocular vision loss in contralateral eye among 17% of patients, bilateral NHR in 17% of patients, posterior pole involvement in 46% of eyes, and involvement > 2 retinal quadrants in 46% of eyes. CONCLUSIONS: The visual prognosis of patients with NHR remains poor. Prompt investigation of immune status and presence of factors justifying intravitreal antiviral injections must be prioritized to initiate and adapt management while awaiting causative virus confirmation.

Influence of treatment with neutralizing monoclonal antibodies on the SARS-CoV-2 nasopharyngeal load and quasispecies.

OBJECTIVES: To evaluate the impact of neutralizing monoclonal antibody (mAb) treatment and to determine whether the selective pressure of mAbs could facilitate the proliferation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with spike protein mutations that might attenuate mAb effectiveness. PATIENTS AND METHODS: We evaluated the impact of mAbs on the nasopharyngeal (NP) viral load and virus quasispecies of mAb-treated patients using single-molecule real-time sequencing. The mAbs used were: Bamlanivimab alone (four patients), Bamlanivimab/Etesevimab (23 patients) and Casirivimab/Imdevimab (five patients). RESULTS: The NP SARS-CoV-2 viral load of mAb-treated patients decreased from 8.2 log10 copies/mL before administration to 4.3 log10 copies/mL 7 days after administration. Five immunocompromised patients given Bamlanivimab/Etesevimab were found to have mAb activity-reducing spike mutations. Two patients harboured SARS-CoV-2 variants with a Q493R spike mutation 7 days after administration, as did a third patient 14 days after administration. The fourth patient harboured a variant with a Q493K spike mutation 7 days post-treatment, and the fifth patient had a variant with a E484K spike mutation on day 21. The emergence of the spike mutation was accompanied by stabilization or rebound of the NP viral load in three of five patients. CONCLUSION: Two-mAb therapy can drive the selection of resistant SARS-CoV-2 variants in immunocompromised patients. Patients given mAbs should be closely monitored and measures to limit virus spread should be reinforced.

Intra-nodal injection of gentamicin for the treatment of suppurated cat scratch disease's lymphadenitis.

PURPOSE: Cat scratch disease (CSD)'s lymphadenitis may have a protracted course with painful suppuration necessitating several needle aspirations or surgical drainage. The objective of this study was to evaluate the benefit of an intra-nodal injection of gentamicin add-on oral azithromycin treatment on the outcome of suppurated CSD's lymphadenitis. METHODS: We performed a retrospective monocentric study including 51 consecutive patients diagnosed between Jan 2009 and Mar 2014 with suppurated CSD who had a positive PCR for Bartonella henselae DNA in pus collected from lymph node by needle aspiration, and who were treated with azithromycin. RESULTS: Among them, 26/51 patients (51%) received oral azithromycin only, of whom 8 patients (31%) were cured and 18 patients (69%) had complications, while 25/51 patients (49%) received an intra-nodal injection of gentamicin add-on oral azithromycin, of whom 16 patients (64 %) were cured and 9 patients (36%) had complications. In univariate analysis, the combined treatment was the only variable related to cure without complications (64 versus 31%, p = 0.01), but this difference did not remain statistically significant in multivariate analysis (OR = 3.84, 95% CI: 0.95-15.56, p = 0.06). CONCLUSIONS: Intra-nodal injection of gentamicin add-on oral azithromycin treatment might improve the outcome of patients with suppurated CSD's lymphadenitis, deserving further randomized studies.

Isolation on Chocolate Agar Culture of Legionella pneumophila Isolates from Subcutaneous Abscesses in an Immunocompromised Patient.

Cutaneous infections due to Legionella species have rarely been reported (L. J. Padrnos, J. E. Blair, S. Kusne, D. J. DiCaudo, and J. R. Mikhael, Transpl Infect Dis 16:307-314, 2014; P. W. Lowry, R. J. Blankenship, W. Gridley, N. J. Troup, and L. S. Tompkins, N Engl J Med 324:109-113, 1991; M. K. Waldor, B. Wilson, and M. Swartz, Clin Infect Dis 16:51-53, 1993). Here we report the identification of Legionella pneumophila isolates, from subcutaneous abscesses in an immunocompromised patient, that grew in an unusual medium for Legionella bacteria.

Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial.

BACKGROUND: Duration of treatment for patients with vertebral osteomyelitis is mainly based on expert recommendation rather than evidence. We aimed to establish whether 6 weeks of antibiotic treatment is non-inferior to 12 weeks in patients with pyogenic vertebral osteomyelitis. METHODS: In this open-label, non-inferiority, randomised controlled trial, we enrolled patients aged 18 years or older with microbiologically confirmed pyogenic vertebral osteomyelitis and typical radiological features from 71 medical care centres across France. Patients were randomly assigned to either 6 weeks or 12 weeks of antibiotic treatment (physician's choice in accordance with French guidelines) by a computer-generated randomisation list of permuted blocks, stratified by centre. The primary endpoint was the proportion of patients who were classified as cured at 1 year by a masked independent validation committee, analysed by intention to treat. Non-inferiority would be declared if the proportion of cured patients assigned to 6 weeks of treatment was not less than the proportion of cured patients assigned to 12 weeks of treatment, within statistical variability, by an absolute margin of 10%. This trial is registered with EudraCT, number 2006-000951-18, and Clinical Trials.gov, number NCT00764114. FINDINGS: Between Nov 15, 2006, and March 15, 2011, 359 patients were randomly assigned, of whom six in the 6-week group and two in the 12-week group were excluded after randomisation. 176 patients assigned to the 6-week treatment regimen and 175 to the 12-week treatment regimen were analysed by intention to treat. 160 (90·9%) of 176 patients in the 6-week group and 159 (90·9%) of 175 of those in the 12-week group met the criteria for clinical cure. The difference between the groups (0·05%, 95% CI -6·2 to 6·3) showed the non-inferiority of the 6-week regimen when compared with the 12-week regimen. 50 patients in the 6-week group and 51 in the 12-week group had adverse events, the most common being death (14 [8%] in the 6-week group vs 12 [7%] in the 12-week group), antibiotic intolerance (12 [7%] vs 9 [5%]), cardiorespiratory failure (7 [4%] vs 12 [7%]), and neurological complications (7 [4%] vs 3 [2%]). INTERPRETATION: 6 weeks of antibiotic treatment is not inferior to 12 weeks of antibiotic treatment with respect to the proportion of patients with pyogenic vertebral osteomyelitis cured at 1 year, which suggests that the standard antibiotic treatment duration for patients with this disease could be reduced to 6 weeks. FUNDING: French Ministry of Health.

Disseminated osteomyelitis or bone metastases of breast cancer: (18)F-FDG-PET/CT helps unravel an unusual presentation.

We present a case wherein striking (18)F-FDG-PET/CT findings initially considered consistent with recurrent disseminated skeletal metastases of breast cancer were later identified as an unusual presentation of disseminated chronic pyogenic osteomyelitis with Staphylococcus aureus and warneri identified on microbiological culture. A 76-year-old female with previous history of breast cancer presented with a 6-month history of pyrexia, myalgia and weight loss. Besides neutrophilia and elevated C-reactive protein, other blood indices, cultures and conventional imaging failed to identify the cause of pyrexia of unknown origin (PUO). (18)F-FDG-PET/CT demonstrated multiple widespread foci of intense FDG uptake in lytic lesions throughout the skeleton. Coupled with previous history of malignancy, findings were strongly suggestive of disseminated metastases of breast cancer. Through targeting an FDG avid lesion, (18)F-FDG-PET/CT aided CT-guided biopsy, which instead identified the lesions as chronic pyogenic osteomyelitis. Following prolonged antibiotic therapy, repeat (18)F-FDG-PET/CT demonstrated significant resolution of lesions. This case demonstrated an unusual presentation of disseminated osteomyelitis on (18)F-FDG-PET/CT and highlighted the use of (18)F-FDG-PET/CT as a trouble shooter in PUO but demonstrated that unusual presentations of benign or malignant pathologies cannot always reliably be differentiated on imaging alone without aid of tissue sampling. Furthermore, this case highlights the potential role (18)F-FDG-PET/CT could provide in assessing response to antibiotic therapy.

In situ evidence of JC virus control by CD8+ T cells in PML-IRIS during HIV infection.

OBJECTIVE: To determine the pathophysiologic features of progressive multifocal leukoencephalopathy (PML) associated with immune reconstitution inflammatory syndrome (PML-IRIS) in HIV-infected patients. METHODS: In a cross-sectional study, we retrospectively analyzed 11 HIV-infected patients with a firm diagnosis of PML-IRIS. Brain biopsies were collected from 5 patients and their histopathologic features were compared to those of 4 HIV-infected patients with classic PML. RESULTS: PML-IRIS developed soon after initiation of antiretroviral therapy in late-presenting HIV-infected patients. The lesions from the 5 biopsied PML-IRIS patients were characterized by a reduction in the density of JC virus (JCV)-infected cells when compared to the 4 patients with PML (11.1 ± 3.2/mm² vs 51.2 ± 4.3/mm², p = 0.01). Comparing the 5 patients with PML-IRIS vs the 4 patients with PML, this correlated with an increased accumulation of CD8+ T cells (818.2 ± 192.8/mm² vs 52.5 ± 10.6/mm², p = 0.01), CD20+ B cells (33.4 ± 13.5/mm² vs 0.5 ± 0.5/mm², p = 0.01), and CD138+ plasma cells (177 ± 84.1/mm² vs 0.25 ± 0.25/mm², p = 0.01), while the number of CD68+ macrophages/microglia did not differ. The ratio between CD8+ T cells and JCV-infected cells was 70 times higher in the 5 patients with PML-IRIS. These findings indicate a clear relationship between an enhanced recruitment of CD8+ T cells and the associated control of the JCV infection. CONCLUSIONS: Our data provide in situ evidence that PML-IRIS brain lesions are enriched in cytotoxic CD8+ T cells that engage JCV-infected oligodendrocytes. This leads to a better control of JCV dissemination, but at the cost of oligodendrocyte cell death and demyelination.

Mycobacterial-immune reconstitution inflammatory syndrome: a cause of acute interstitial nephritis during HIV infection.

Kidney injury during HIV infection encompasses a wide variety of disorders, including acute interstitial nephritis. We report a case of acute granulomatous interstitial nephritis related to a mycobacterial-triggered immune reconstitution inflammatory syndrome (IRIS) in an HIV-infected patient. IRIS is an emerging health concern during HIV infection and should be considered in the diagnostic frame of acute renal failure during immune restoration.