Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant recipients (SOT) is controversial. To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection. A systematic review and individual patient data meta-analysis. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023. (i) risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (ii) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis. SOT recipients. TMP-SMX prophylaxis versus no prophylaxis. ROBINS-E for comparative studies; dedicated tool for non-comparative studies. For our primary outcome (i.e., to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using the GRADE approach. Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis, 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR=0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100). In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.

Objectives: Hepatitis C virus (HCV) is the major cause of cryoglobulinemia. Direct-acting antivirals (DAAs) have markedly changed the therapeutic outcomes in the treatment of patients with HCV. We evaluate the efficacy, safety, immunological, and clinical response of different DAA regimens in HCV-cryoglobulinemia.Patients and methods: Ninety-three cryoglobulinemic patients, divided into symptomatic [symptomatic cryoglobulinemic patients (SCP;n=35)] and asymptomatic [nonsymptomatic cryoglobulinemic patients (NSCP;n=60)], underwent DAAs. Eighty-nine comparable noncryoglobulinemic patients were selected as a control group. We evaluated the sustained virological response (SVR), the adverse effects, and the immune and symptomatic response.Results: Percentages of patients who achieved SVR and experienced adverse effects were not statistically different between the three groups (100, 95, 93.3% and 57.1, 53.3, 48.3%). In 68.5% of SCP and in 76.7% of NSCP, cryoglobulins disappeared at SVR. No risk factor was associated with the persistence of cryoglobulins. An increase was observed both in C4 (P=0.002;P=0.018) and in C3 (P=0.0037;P=0.031) in SCP and NSCP. About 70% of symptomatic patients showed a complete or partial symptomatic remission: persistence of symptoms is correlated to the type of clinical picture.Conclusion: DAA regimens are safe and effective in patients with HCV-cryoglobulinemia. The achievement of SVR is necessary, but not sufficient, to achieve a complete immunological and clinical response.

(Background) The diagnosis and the antimicrobial treatment of orthopedic infection are challenging, especially in cases with culture-negative results. New molecular methods, such as next-generation sequencing (NGS), promise to overcome some limitations of the standard culture, such as the detection of difficult-to-grow bacteria. However, data are scarce regarding the impact of molecular techniques in real-life scenarios. (Methods) We included cases of suspected orthopedic infection treated with surgery from May 2021 to September 2023. We combined traditional cultures with NGS. For NGS, we performed a metagenomic analysis of ribosomal 16s, and we queried dedicated taxonomic libraries to identify the species. To avoid false positive results, we set a cut-off of 1000 counts of the percentage of frequency of reads. (Results) We included 49 patients in our study. Our results show the presence of bacteria in 36/49 (73%) and 29/49 (59%) cases studied with NGS and traditional cultures, respectively. The concordance rate was 61%. Among the 19/49 discordant cases, in 11/19 cases, cultures were negative and NGS positive; in 4/19, cultures were positive and NGS negative; and in the remaining 4/19, different species were detected by traditional cultures and NGS. (Conclusions) Difficult-to-grow microorganisms, such as slow-growing anaerobic bacteria, were better detected by NGS compared to traditional culture in our study. However, more data to distinguish between true pathogens and contaminants are needed. NGS can be an additional tool to be used for the diagnosis of orthopedic infections and the choice of appropriate antimicrobial therapy.

Recent data suggest that oral therapy can be effective for bone infections. We aim to assess the efficacy of an early switch to oral therapy (<2 weeks) compared to a non-early switch in bacterial native vertebral osteomyelitis. We conducted a cohort study at Mayo Clinic, Rochester (MN), between 2019–2021 combined with a systematic review, which queried multiple databases. Data were analyzed using a random-effects model. The cohort study included 139 patients: two received an early switch. Of 3708 citations, 13 studies were included in the final analysis. Meta-analysis demonstrated no difference in treatment failure (odds ratio = 1.073, 95 % confidence interval 0.370–3.116), but many studies presented high risk of bias. Current evidence is insufficient to conclude the proportion of patients with failure or relapse is different in the two groups. High-quality studies are warranted before early switch can be routinely recommended.

We report the case of a 61-year-old patient with a history of prostate cancer affected by bone metastasis. He presented to our attention for ulcerous and necrotic cutaneous lesions unresponsive to antibiotics. The spread of cutaneous lesions and the onset of neurological symptoms suggested a cryptococcal disease, which was confirmed by lumbar puncture and cutaneous biopsy. We present the diagnostic and therapeutic approach to this case.